UM PAINEL DE CARACTERÍSTICAS CLÍNICAS E NEUROPATOLÓGICAS DA DOENÇA CEREBROVASCULAR ATRAVÉS DOS NOVOS MÉTODOS DE NEUROIMAGEM

Autoria SCIMAGO INSTITUTIONS RANKINGS

A última década vem testemunhando avanços substanciais na aquisição de marcadores biológicos para o diagnóstico da doença cerebrovascular (DCV). Os métodos de neuroimagem avançados não apenas fornecem uma contribuição estratégica para o diagnóstico diferencial do comprometimento cognitivo vascular (VCI) e demência vascular (VaD), mas contribuem substancialmente na elucidação dos mecanismos fisiopatológicos relacionados à doença de vasos pequenos (SVD) e sua progressão clínica.

Objetivo: Nesta revisão, métodos de imagem estruturais e metabólicos foram descritos e sua importância diagnóstica analisada, particularmente na investigação da CVD relacionada ao envelhecimento. Métodos: uma pesquisa eletrônica de janeiro de 2010 a 2017 foi realizada através do PubMed/MEDLINE, do Instituto de Informação Científica Web of Knowledge e da EMBASE.

Resultados: O emprego de estudos de multimodalidade plenamente funcional com Ressonância Magnética (MR)/ Tomografia por Emissão de Pósitrons (PET) representa uma janela para a caracterização clínica mais detalhada da VCI-VaD; com relação à neuroimagem estrutural, a ressonância magnética em 3,0 T vem permitindo varreduras com maior resolução e matrizes de imagem mais elevadas, cortes mais delgados e maior detalhamento anatômico das lesões vasculares.

Conclusão: Embora a importância da maior parte dessas técnicas no cenário clínico aguarde reconhecimento, há uma grande expectativa de que o seu uso favoreça intervenções terapêuticas progressivamente mais precoces e refinadas para o gerenciamento efetivo do VCI-VaD.

Palavras-chave:
neuroimagem; vascular; PET; ressonância magnética; imagem de tensor de difusão; DTI; métodos inovadores

Authors (sample)	Subjects (Mean age/Gender M:F)					Methods	Neuroimaging method	Neuroimaging vs behavioral changes
Lanna et al. 2012¹⁰⁴ (n=6)	Patients (n=6) 61.3/2:4					Clinical/neuropsychological and brain MRI/SPECT examination.	1.5T MRI; SPECT with IV line 740MBq of (99 m) Tc.	Moderate to severe dementia associated with strategic strokes as a result of neuronal disruption in multimodal areas.
Holst et al. 2012¹⁰⁵ (n=440)	SVD no dementia (n=440) 65.2/239:201					Clinical/ neuropsychological and brain MRI/DTI examination.	1.5T MRI; DTI processing.	Microstructural integrity of the cingulum is specifically related to episodic memory function, notably verbal memory, in non-demented elderly with SVD. Cingulum integrity is significantly lower in participants with greater hippocampal alteration than those with hippocampal integrity.
Hilal et al. 2016¹⁰⁶ (n=424)	NCI (n=96) 68.4/44:52	CIND (n=177) 71.5/91:86 CIND (n=107) VCIND (n=70)	Dementia (n=151) 76.1/57:94 Alzheimer (n=121) VaD (n=30)			Clinical/neuropsychological MRI/MRA examination.	3.0T MRI; 3D TOF MRA.	ICS was shown to be independently associated with VCIND, whereas in dementia, this association was mediated by cerebral ischemic damage, independently of cardiovascular risk factors. This further suggests that ICS is a marker of cerebral or generalized atherosclerosis and may be a viable treatment target.
Lawrence et al. 2013⁶² (n=165)	SVD (n=115) 70.0/78:37	Control (n=50) 70.3/35:22				Clinical/neuropsychological and brain MRI/DTI examination.	1.5T MRI; DTI processing.	Patients with symptomatic SVD and radiological leukoaraiosis exhibited greater impaired performance in executive function, processing speed and working memory than in episodic memory. Executive memory and processing speed were associated with lacunar infarct load, reduced brain volume, and microstructural WM alterations (DTI)
Liu et al. 2014⁶⁵ (n=69)	SIVD (n=34) 69.0/21:13	Control (n=35) 68.0/22:13				Clinical/neuropsychological and brain MRI examination.	3T MRI 1.0 mm.	Cortical thinning of the hippocampus and volume reduction of the caudate nucleus was associated with poorer global cognitive performance in SIVD patients. Cortical thinning and cognitive decline were not related to severity of WML. The automated measures of deep gray matter also revealed significant volume reductions in the amygdala and nucleus accumbens.
Cavallari et al. 2014¹⁰⁷ (n=56)	Subjects (n=56) 82/24:32					Clinical/neuropsychological and brain MRI/DTI examination.	3T MRI; DTI processing.	The observed association between DTI changes in the thalamus at baseline and the rate of WMH accrual singles out thalamic FA as a promising candidate surrogate marker of cerebral SVD progression, and points to a possible causal role of thalamic damage in the accrual of WMHs.
Guerra et al. 2014¹⁰⁸ (n=25)	SIVD (n=7) 78.1/02:05	Control (n=9) 75.0/03:06	AD (n=9) 74.3/00:09			Clinical/neuropsychological TMS mapping.	TMS mapping.	SIVD patients showed higher degree of WMH and lesser extent of medial temporal atrophy than AD patients
Jeong et al. 2014¹⁰⁹ (n=587)	END (n=79) 64.4/44:35	No END (n=508) 65.5/303:205				Clinical/neuropsychological and brain MRI examination.	1.5T or 3T MRI.	SSSIs who exhibited relevant artery stenosis and branch atheromatous lesions were more likely to develop END but the association was not documented in the SSSI patients with WMH, old lacunar infarctions, or CMBs.
Garriga et al. 2015¹¹⁰ (n=105)	MCI (n=50) 72.0/26:24	VaD (n=6) 73.0/03:03	AD (n=31) 76.0/12:19	LBD (n=6) 73.0/03:03	PDD (n=12) 77.0/10:02	Clinical/neuropsychological MRI or CT and ¹²³I-FP-CIT SPECT examination.	1.5T MRI; CT and ¹²³I-FP-CIT SPECT.	¹²³I-FP-CIT SPECT is a useful tool to discriminate MCI from overall dementia subtypes. However, ¹²³I-FP-CIT SPECT could not discriminate among different dementia types.
Lin et al. 2015¹¹¹ (n=50)	VCIND (n=22) 72.8/14:08	Control (n=28) 70.9/16:12				Clinical/neuropsychological and brain DTI examination.	3.0T MR DTI processing.	SIVD patients displayed abnormal WM connectivity in all supratentorial regions, involving projection, association, and commissural fibers; the severity of damage in WM tracts was correlated with cognitive dysfunction in SIVD patients.
Ostojic et al. 2015¹¹² (n=50)	VD (n=25) 69.5/16:09	Control (n=25) 71.6/15:10				Clinical/neuropsychological and brain MRI/DTI examination.	3T MRI; DTI processing.	No significant group differences for FA were found in the left and right hippocampus; no significant differences between hemispheres in either HC and VD group were reported.
Wu et al. 2015¹¹³ (n=60)	SIVD (n=30) 65.3/17:13	Control (n=30) 63.9/16:14				Clinical/neuropsychological and brain MRI/DTI examination.	1.5T MRI; DTI processing.	SIVD patients had significantly reduced corpus callosum size compared with healthy controls. Patients with SIVD showed significantly lower FA values in the genu and splenium of the corpus callosum as compared with healthy controls.
Baykara et al. 2016⁸⁹ (n=710)	CADASIL exploratory (n=113) 49.1/43:61	CADASIL validation (n=57) 53.4/38:19	Sporadic SVD (n=444) 65.3/243:201	Memory clinic patients with SVD (n=105) 74.9/54:51		Clinical/neuropsychological and brain MRI/DTI/PSMD examination.	MRI; DTI with PSMD processing.	The study established a novel-imaging marker (PSMD) for SVD. PSMD combined the analysis of DTI-WM tract skeletonization and MD histogram; PSMD was associated with SVD pathology but not with neurodegenerative pathology. An important association between PSMD and processing speed deficits across all study samples was reported.
Veluw et al. 2016⁵⁹ (n=5)	Cases with CAA (n=5) 85.0/03:02					Clinical/neuropsychological and brain histopathological and in vivo and ex vivo MRI examination.	Ex vivo 7.0T MRI.	CMBs and microinfarcts appeared to be the most frequent marker of focal bleeding and focal ischaemic injury in SVD (particularly CAA), and therefore are important candidate biomarkers for clinical trials.
Thong et al. 2014⁸⁷ (n=100)	Control (n=25) 68.00/11:14	Mild VCIND (n=25) 66.20/19:06	MSVCI (n=30) 69.87/14:16	AD (n=20) 74.25/06:14		Clinical/neuropsychological and brain MRI/HARDI examination.	3T MRI 1 mm and HARDI 3 mm.	Compared to the Mild VCIND group, MSVCI subjects showed thinner cortex in the left superior frontal gyrus, cingulate, temporal pole, and middle temporal gyrus; in contrast, no statistical differences between groups in cortical thickness in the right hemisphere were reported.
Mascalchi et al. 2016¹¹⁴ (n=36)	CADASIL (n=18) 42.9/07:11	Control (n=18) 41.2/10:8				Clinical/neuropsychological and brain MRI/DTI examination.	3T MRI ; 1mm ; DTI processing; TBSS.	CADASIL patients showed extensive almost symmetric areas of significantly increased radial and mean diffusivities and of significantly decreased axial diffusivity and FA that involved the cerebral WM, the thalami, and the corpus callosum.
Pasi et al. 2017¹¹⁵ (n=36)	CAA-ICH (n=191) 74.9/95:96	HTN-ICH (n=125) 66.1/73:52				Clinical/neuropsychological and brain MRI examination.	1.5T MRI.	The topographic distribution of lacunes (lobar vs deep) helped distinguish the underlying SVD subtype (CAA vs HTN-SVD) in patients with primary ICH, regardless of age status, diagnosis of hypertension or other MRI markers of SVD severity. Lobar lacunes seemed to have a closer relationship with WMH, suggesting a possible common origin.

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E-mail: revistadementia@abneuro.org.br | demneuropsy@uol.com.br

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[TFN1] AD: Alzheimer's Disease; MRI: Magnetic Resonance Imaging; DTI: Diffusion Tensor Imaging; TBSS: Tract-Based Spatial Statistics; TMS: Transcranial Magnetic Stimulation; FA: Fractional Anisotropy; WM: White Matter; WMH: White Matter Hyperintensities; CC: corpus callosum; SPECT: Single Photon Emission Computed Tomography; IV: intravenous; VCIND: Vascular Cognitive Impairment, No Dementia; CIND: Cognitive Impairment, No Dementia; NCI: No Cognitive Impairment; 3D TOF MRA: Three-dimensional Time-of-flight Magnetic Resonance Angiography Images; END: Early Neurological Deterioration; SIVD: Subcortical Ischaemic Vascular Dementia; SSSIs: Single Small Subcortical Infarctions; SVD: Small Vessel Disease; PDD: Parkinson Disease With Dementia; LBD: Lewy Body Dementia; ICH: Intracerebral Hemorrhage; HTN-SVD: Hypertensive Small Vessel Disease; PSMD: Peak width of skeletonized mean diffusivity; HARDI: High Angular Resolution Diffusion Imaging;

[TFN2] * gender not discriminated,

[TFN3] ** age not discriminated,

[TFN4] ** Mean Age and gender were not described, but no significant differences were found between groups regarding these parameters.