The role of biopsies and autopsies in the diagnosis of cognitive impairment, with emphasis on small vessel diseases: A critical appraisal enriched by personal experience

Views & Reviews Dement Neuropsychol 2017 December;11(4):356-363 DOI: 10.1590/1980-57642016dn11-040004 The role of biopsies and autopsies in the diagnosis of cognitive impairment, with emphasis on small vessel diseases A critical appraisal enriched by personal experience Leila Chimelli1 ABSTRACT. Acquired and hereditary microangiopathies cause cerebral small vessel diseases (CSVD) that impair cognition. The most frequent is primary angiitis of the CNS (PACNS), whose diagnosis remains challenging, requiring a multidisciplinary approach. Secondary vasculitis, CADASIL, miscellaneous microangiopathies and lymphomas, also cause cognitive impairment. Despite the fact that the need for biopsy has decreased in the era of new neuroimaging methods, biopsies that include small leptomeningeal and parenchymal arterial vessels still remain the gold standard to diagnose PACNS and other CSVD, and to exclude mimics such as infections and malignancies. New approaches for pathological consequences relevant to vascular cognitive impairment such as silent brain lesions, microinfarcts, microbleeds and subtle loss of microstructural integrity, may be detected in autopsies. This article addresses the role of biopsies and autopsies for the diagnosis of cognitive impairment related to small vessel diseases or other inflammatory/ischemic processes, and presents a critical appraisal based on personal experience. Key words: cognitive impairment, cerebral small vessel diseases, vasculitis, cerebral and meningeal biopsy, autopsy. O PAPEL DAS BIÓPSIAS E AUTÓPSIAS NO DIAGNÓSTICO DA DEFICIÊNCIA COGNITIVA, COM ÊNFASE NAS DOENÇAS CEREBRAIS DE PEQUENOS VASOS: AVALIAÇÃO CRÍTICA E EXPERIÊNCIA PESSOAL RESUMO. As microangiopatias adquiridas e hereditárias causam doenças cerebrais de vasos pequenos, que comprometem a cognição. A mais frequente é a vasculite primária do sistema nervoso central, cujo diagnóstico continua desafiador, exigindo abordagem multidisciplinar. Vasculite secundária, CADASIL, microangiopatias diversas e linfomas também causam deficiência cognitiva. Apesar da necessidade de biópsia ter diminuído na era de novos métodos de neuroimagem, as biópsias que incluem pequenos vasos arteriais leptomeníngeos e parenquimatosos continuam sendo o padrão-ouro para o diagnóstico de vasculites primárias, afastando situações que as mimetizam, como infecções e neoplasias. Novas abordagens sobre as alterações teciduais de origem vascular relevantes para comprometimento cognitivo, como lesões cerebrais silenciosas, microinfartos, microssangramentos e perda leve de integridade micro estrutural, podem ser detectadas em autópsias. Este artigo aborda o papel das biópsias e autópsias para o diagnóstico do comprometimento cognitivo associado a doenças cerebrais de pequenos vasos ou outros processos inflamatórios/isquêmicos, e apresenta uma avaliação crítica baseada em experiência pessoal. Palavras-chave: déficit cognitivo, doenças cerebrais de pequenos vasos, vasculite, biópsia cerebral e meníngea, autópsia. INTRODUCTION I n its broadest sense, “microcirculation” includes parenchymal and leptomeningeal arterioles, venules, and capillaries. Arbitrarily, CNS small vessels are defined as small veins and perforating arteries derived from the circle of Willis with diameters ranging from 40 to 400 µm.1 This study was conducted at the Instituto Estadual do Cérebro Paulo Niemeyer – Laboratory of Neuropathology, Rio de Janeiro RJ – Brazil. 1 Instituto Estadual do Cérebro Paulo Niemeyer – Laboratory of Neuropathology and Universidade Federal do Rio de Janeiro – Pathology Department, Rio de Janeiro, RJ – Brazil. Leila Chimelli. MD, PhD. Laboratory of Neuropathology / Instituto Estadual do Cérebro Paulo Niemeyer – Rua do Resende 156 / Centro – 20231-092 Rio de Janeiro RJ – Brazil. E-mail - . Disclosure: The author reports no conflicts of interest. Received November 21, 2017. Accepted in final form November 22, 2017. 356 Small vessel diseases: biopsies, autopsies and cognitive impairment     Chimelli Dement Neuropsychol 2017 December;11(4):356-363 “Cerebral Small Vessel Diseases (CSVD)” or microangiopathies involve intraparenchymal vessels, including predominantly arterioles, mostly end arteries with limited collateral anastomoses up to the capillary network. Exceptions to this rule are some vasculites involving larger vessels, which are conventionally included within this group of conditions. CSVD are associated with a variety of ischemic and/or hemorrhagic manifestations. Cerebral microangiopathies such as arteriolosclerosis, lipohyalinosis and cerebral amyloid angiopathy (CAA), commonly produce intraparenchymal hemorrhage, but arteriosclerosis and lipohyalinosis are also associated with cerebral infarcts, especially small lacunar infarcts; CAA is also occasionally associated with ischemic lesions.2,3 The development of new neuroimaging methods has enhanced awareness of these important causes of neurologic morbidity. Correlation between neuroimaging data and neuropathology is important and may help identify characteristic patterns of abnormality such as small hemorrhages, microbleeds, lacunes, status cribrosus and secondary changes in white matter (leukoencephalopathies). CSVD associated with cognitive impairment/dementia. Ischemic lesions within subcortical white matter, as well as secondary leukoencephalopathies resulting from necrosis of adjacent tissue, may contribute to cognitive impairment and dementia. Though dementia may result from widespread arteriosclerosis or CAA in the brain, and be associated with varying degrees of cerebral ischemia, two distinct entities should be considered in this context: Binswanger’s subcortical arteriosclerotic leukoencephalopathy (BSL) and Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL).1,3-5 BSL is a disease of elderly hypertensive patients, char- acterized by a slowly progressive condition, typically showing stepwise deterioration and episodes of partial recovery. Disorders of memory, mood, and cognition, as well as occasional focal motor signs and less commonly, a pseudobulbar syndrome in association with deterioration of gait and loss of sphincter control, can be observed. The brain may show asymmetric poorly delineated regions of leukomalacia, lacunar infarcts in the centrum semiovale, with preservation of the overlying cerebral cortex. Histology of white matter shows thickened arteries with an ‘onion skin’ appearance and scattered chronic inflammation with macrophage/microglial infiltrate around blood vessels. Transition between relatively preserved white matter (containing sclerotic arteries with severe adventitial fibrosis), diffuse myelin pallor, sometimes poorly defined white matter cavitation, and gliosis may be seen. Meningeal arteries are sometimes surrounded by hemosiderin, suggesting previous hemorrhage.3 CADASIL resembles BSL, but is distinguished by its familial nature and the deposition of abnormal ma (...truncated)