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. 2023 Nov;81(11):989-999.
doi: 10.1055/s-0043-1772834. Epub 2023 Nov 30.

Intracranial hemorrhages in patients with COVID-19: a systematic review of the literature, regarding six cases in an Amazonian population

William de Sousa Lima  1 , Marcelo Henrique Pereira Soares  1 , Eric Homero Albuquerque Paschoal  1 , Joelma Karin Sagica Fernandes Paschoal  1 , Fernando Mendes Paschoal Jr  1 , Edson Bor-Seng-Shu  2
Affiliations

Intracranial hemorrhages in patients with COVID-19: a systematic review of the literature, regarding six cases in an Amazonian population

William de Sousa Lima et al. Arq Neuropsiquiatr. 2023 Nov.

Abstract
in English, Portuguese

Background: Coronavirus disease 2019 (COVID-19) has emerged as a public health emergency worldwide, predominantly affecting the respiratory tract. However, evidence supports the involvement of extrapulmonary sites, including reports of intracranial hemorrhages.

Objective: To describe six original cases and review the literature on intracranial hemorrhages in patients diagnosed with COVID-19 by molecular methods.

Methods: A systematic literature review was performed on MEDLINE, PubMed, and NCBI electronic databases to identify eligible studies. Of the total 1,624 articles retrieved, only 53 articles met the inclusion criteria.

Results: The overall incidence of intracranial hemorrhage in patients hospitalized for COVID-19 was 0.26%. In this patient group, the mean age was 60 years, and the majority were male (68%) with initial respiratory symptoms (73%) and some comorbidity. Before the diagnosis of hemorrhage, 43% of patients were using anticoagulants, 47.3% at therapeutic doses. The intraparenchymal (50%) was the most affected compartment, followed by the subarachnoid (34%), intraventricular (11%), and subdural (7%). There was a predominance of lobar over non-lobar topographies. Multifocal or multicompartmental hemorrhages were described in 25% of cases. Overall mortality in the cohort studies was 44%, while around 55% of patients were discharged from hospital.

Conclusion: Despite the unusual association, the combination of these two diseases is associated with high rates of mortality and morbidity, as well as more severe clinicoradiological presentations. Further studies are needed to provide robust evidence on the exact pathophysiology behind the occurrence of intracranial hemorrhages after COVID-19 infection.

Antecedentes: A COVID-19 emergiu como uma emergência de saúde pública em todo o mundo, proporcionando lesão principalmente do trato respiratório. No entanto, várias evidências apontam para acometimento de sítios extrapulmonares, incluindo relatos de hemorragias intracranianas.

Objetivo: Descrever seis casos originais e revisar a literatura sobre hemorragias intracranianas em pacientes com diagnostico de COVID-19 por métodos moleculares. MéTODOS: A revisão sistemática da literatura foi feita nas bases de dados eletrônicas da MEDLINE, PubMed e NCBI para identificar os estudos elegíveis. Do total de 1.624 artigos recuperados, apenas 53 artigos preencheram os critérios de inclusão.

Resultados: A incidência geral de hemorragia intracraniana nos pacientes internados por COVID-19 foi de 0,26%. A média de idade foi de 60 anos, e a maioria dos pacientes era do sexo masculino (68%) com sintomas respiratórios iniciais (73%) e alguma comorbidade. Antes do diagnóstico de hemorragia, 43% estavam em uso de anticoagulantes, 47,3% destes em doses terapêuticas. O compartimento mais acometido foi o intraparenquimatoso (50%), seguido do subaracnoideo (34%), intraventricular (11%) e subdural (7%). Houve predomínio de topografias lobares sobre as não-lobares. Hemorragias multifocais ou multicompartimentais foram descritas em 25% dos casos. A mortalidade geral nos estudos de coorte foi de 44%, enquanto houve alta hospitalar em cerca de 55% dos pacientes. CONCLUSãO: Apesar da associação incomum, a combinação dessas doenças está relacionada com altas taxas de mortalidade e morbidade, bem como apresentações clínico-radiológicas mais graves. Mais estudos são necessários para oferecer evidências robustas sobre a fisiopatologia exata por trás da ocorrência de hemorragias intracranianas após infecção por COVID-19.

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Conflict of interest statement

The authors have no conflict of interests to declare.

Figures

Figure 1
Figure 1
PRISMA flow diagram of included articles. Source: PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. BMJ. 2021;372:n71. DOI: 10.1136/bmj.n71. Available from: http://www.prisma-statement.org/ .
Figure 2
Figure 2
Intraparenchymal hemorrhages. (A-B) Patient 1: 66 years-old male presenting with decreased level of consciousness. Axial non-contrast CT images ( A ) showing an intraparenchymal hemorrhage in temporal lobe region with left to right midline shift and ( B ) extension to fourth ventricle in association with left cerebellar hemorrhage. Patient 2: 59-year-old female presenting with seizures and decreased level of consciousness. Axial and sagittal non-contrast CT images ( C-D ) demonstrating an extensive intraparenchymal hemorrhage involving left basal ganglia and temporoparietal areas with a left to right midline shift and extension to posterior horn of left lateral ventricle, associated with ventricular dilatation of posterior horns of lateral ventricles.
Figure 3
Figure 3
Hemorrhagic transformation of cerebral venous thrombosis (CVT). ( A-D ) Patient 4: 39-year-old female presenting with severe progressive headache. Axial non-contrast CT images ( A ) demonstrating the “cord sign” (black arrow) indicating thrombosis of cerebral cortical veins; and ( B ): intraparenchymal hemorrhage in left parietal lobe with left-to-right midline shift. Transcranial doppler ( C-D ) shows spectral image with spikes on middle cerebral artery monitoring, indicating cerebral circulatory collapse.
See this image and copyright information in PMC

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