Dataset Information

Structural neuroimaging differentiates vulnerability from disease manifestation in colombian families with Huntington's disease.

ABSTRACT:

Introduction

The volume of the striatal structures has been associated with disease progression in individuals with Huntington's disease (HD) from North America, Europe, and Australia. However, it is not known whether the gray matter (GM) volume in the striatum is also sensitive in differentiating vulnerability from disease manifestation in HD families from a South-American region known to have high incidence of the disease. In addition, the association of enlarged brain perivascular spaces (PVS) with cognitive, behavioral, and motor symptoms of HD is unknown.

Materials and methods

We have analyzed neuroimaging indicators of global atrophy, PVS burden, and GM tissue volume in the basal ganglia and thalami, in relation to behavioral, motor, and cognitive scores, in 15 HD patients with overt disease manifestation and 14 first-degree relatives not genetically tested, which represent a vulnerable group, from the region of Magdalena, Colombia.

Results

Poor fluid intelligence as per the Raven's Standard Progressive Matrices was associated with global brain atrophy (p = 0.002) and PVS burden (p ? 0.02) in HD patients, where the GM volume in all subcortical structures, with the exception of the right globus pallidus, was associated with motor or cognitive scores. Only the GM volume in the right putamen was associated with envy and MOCA scores (p = 0.008 and 0.015 respectively) in first-degree relatives.

Conclusion

Striatal GM volume, global brain atrophy and PVS burden may serve as differential indicators of disease manifestation in HD. The Raven's Standard Progressive Matrices could be a cognitive test worth to consider in the differentiation of vulnerability versus overt disease in HD.

SUBMITTER: Valdes Hernandez MDC

PROVIDER: S-EPMC6710228 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Structural neuroimaging differentiates vulnerability from disease manifestation in colombian families with Huntington's disease.

Valdés Hernández Maria Del C MDC Abu-Hussain Janna J Qiu Xinyi X Priller Josef J Parra Rodríguez Mario M Pino Mariana M Báez Sandra S Ibáñez Agustín A

Brain and behavior 20190705 8

<h4>Introduction</h4>The volume of the striatal structures has been associated with disease progression in individuals with Huntington's disease (HD) from North America, Europe, and Australia. However, it is not known whether the gray matter (GM) volume in the striatum is also sensitive in differentiating vulnerability from disease manifestation in HD families from a South-American region known to have high incidence of the disease. In addition, the association of enlarged brain perivascular spa ...[more]

PMID: 31276317

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Project description:Huntington's disease can be predicted many years before symptom onset, and thus makes an ideal model for studying the earliest mechanisms of neurodegeneration. Diffuse patterns of structural connectivity loss occur in the basal ganglia and cortex early in the disease. However, the organizational principles that underlie these changes are unclear. By understanding such principles we can gain insight into the link between the cellular pathology caused by mutant huntingtin and its downstream effect at the macroscopic level. The 'rich club' is a pattern of organization established in healthy human brains, where specific hub 'rich club' brain regions are more highly connected to each other than other brain regions. We hypothesized that selective loss of rich club connectivity might represent an organizing principle underlying the distributed pattern of structural connectivity loss seen in Huntington's disease. To test this hypothesis we performed diffusion tractography and graph theoretical analysis in a pseudo-longitudinal study of 50 premanifest and 38 manifest Huntington's disease participants compared with 47 healthy controls. Consistent with our hypothesis we found that structural connectivity loss selectively affected rich club brain regions in premanifest and manifest Huntington's disease participants compared with controls. We found progressive network changes across controls, premanifest Huntington's disease and manifest Huntington's disease characterized by increased network segregation in the premanifest stage and loss of network integration in manifest disease. These regional and whole brain network differences were highly correlated with cognitive and motor deficits suggesting they have pathophysiological relevance. We also observed greater reductions in the connectivity of brain regions that have higher network traffic and lower clustering of neighbouring regions. This provides a potential mechanism that results in a characteristic pattern of structural connectivity loss targeting highly connected brain regions with high network traffic and low clustering of neighbouring regions. Our findings highlight the role of the rich club as a substrate for the structural connectivity loss seen in Huntington's disease and have broader implications for understanding the connection between molecular and systems level pathology in neurodegenerative disease.

Project description:ObjectiveCoronavirus Disease 2019 (COVID-19) initially thought to be confined to the respiratory system only, is now known to be a multisystem disease. It is critical to be aware of and timely recognize neurological and neuroradiological manifestations affecting patients with COVID-19, to minimize morbidity and mortality of affected patients.MethodsWe performed a retrospective chart review of patients admitted to our Level 1 trauma and stroke center during the peak of the COVID-19 outbreak in New York from March 1st to May 30, 2020, with a positive test for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) who presented mainly with neurological findings and had acute radiological brain changes on Computed Tomography (CT) scan. Patients with known chronic neurological disease processes were excluded from the study. We obtained and reviewed demographics, complete blood count, metabolic panel, D-dimer, inflammatory markers such as erythrocyte sedimentation rate (ESR), C reactive protein (CRP), imaging, and patient's hospital course. We reviewed the current literature on neuroimaging, pathophysiology, and their clinical correlations on COVID-19. This case series study was approved by our institutional review board.ResultA total of 16 patients were selected for our case series. The most common neuroimaging features on CT, were territorial to multifocal ischemic infarcts, followed by a combination of ischemia and acute white matter encephalopathic changes, followed by temporal lobe predominant focal or more generalized encephalopathy with both confluent and non-confluent patterns, isolated cortical or more extensive intracranial hemorrhages and some combination of ischemia or hemorrhage and white matter changes. All our patients had severe acute respiratory distress syndrome (ARDS), most of them had elevated inflammatory markers, and D dimer.ConclusionCOVID-19 infection is a multi-organ disease, which can manifest as rapidly progressive neurological disease beyond the more common pulmonary presentation. Early recognition of various neurological findings and neuroimaging patterns in these patients will enable timely diagnosis and rapid treatment to reduce morbidity and mortality. Our retrospective study is limited due to small non-representative sample size, strict selection criteria likely underestimating the true extent of neurological manifestations of COVID-19, mono-modality imaging technique limited to predominantly CT scans and lack of CSF analysis in all except one patient. Multi-institutional, multi-modality, largescale studies are needed with radio-pathological correlation to better understand the complete spectrum of neurologic presentations in COVID-19 patients and study the causal relationship between SARS-CoV-2 and CNS disease process.

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Project description:Background Preclinical and pathology evidence suggests an involvement of brain dopamine (DA) circuitry in Alzheimer’s disease (AD). We in vivo investigated if, when, and in which target regions [123I]FP-CIT-SPECT regional binding and molecular connectivity are damaged along the AD course. Methods We retrospectively selected 16 amyloid-positive subjects with mild cognitive impairment due to AD (AD-MCI), 22 amyloid-positive patients with probable AD dementia (AD-D), and 74 healthy controls, all with available [123I]FP-CIT-SPECT imaging. We tested whether nigrostriatal vs. mesocorticolimbic dopaminergic targets present binding potential loss, via MANCOVA, and alterations in molecular connectivity, via partial correlation analysis. Results were deemed significant at p < 0.05, after Bonferroni correction for multiple comparisons. Results We found significant reductions of [123I]FP-CIT binding in both AD-MCI and AD-D compared to controls. Binding reductions were prominent in the major targets of the ventrotegmental-mesocorticolimbic pathway, namely the ventral striatum and the hippocampus, in both clinical groups, and in the cingulate gyrus, in patients with dementia only. Within the nigrostriatal projections, only the dorsal caudate nucleus showed reduced [123I]FP-CIT binding, in both groups. Molecular connectivity assessment revealed a widespread loss of inter-connections among subcortical and cortical targets of the mesocorticolimbic network only (poor overlap with the control group as expressed by a Dice coefficient ≤ 0.25) and no alterations of the nigrostriatal network (high overlap with controls, Dice coefficient = 1). Conclusion Local- and system-level alterations of the mesocorticolimbic dopaminergic circuitry characterize AD, already in prodromal disease phases. These results might foster new therapeutic strategies for AD. The clinical correlates of these findings deserve to be carefully considered within the emergence of both neuropsychiatric symptoms and cognitive deficits. Supplementary Information The online version contains supplementary material available at 10.1186/s13195-021-00925-1.

Dataset Information

Structural neuroimaging differentiates vulnerability from disease manifestation in colombian families with Huntington's disease.

Introduction

Materials and methods

Results

Conclusion

Publications

Structural neuroimaging differentiates vulnerability from disease manifestation in colombian families with Huntington's disease.

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