Newly recognized cerebral infarctions on postmortem imaging: a report of three cases with systemic infectious disease
© The Author(s). 2017
Received: 9 May 2016
Accepted: 22 December 2016
Published: 10 January 2017
Postmortem imaging (PMI) refers to the imaging of cadavers by computed tomography (CT) and/or magnetic resonance imaging (MRI). Three cases of cerebral infarctions that were not found during life but were newly recognized on PMI and were associated with severe systemic infections are presented.
An 81-year-old woman with a pacemaker and slightly impaired liver function presented with fever. Imaging suggested interstitial pneumonia and an iliopsoas abscess, and blood tests showed liver dysfunction and disseminated intravascular coagulation (DIC). Despite three-agent combined therapy for tuberculosis, she died 32 days after hospitalization. PMI showed multiple fresh cerebral and cerebellar infarctions and diffuse ground-glass shadows in bilateral lungs. On autopsy, the diagnosis of miliary tuberculosis was made, and non-bacterial thrombotic endocarditis that involved the aortic valve may have caused the cerebral infarctions.
A 74-year-old man on steroid therapy for systemic lupus erythematosus presented with severe anemia, melena with no obvious source, and DIC. Imaging suggested intestinal perforation. The patient was treated with antibiotics and drainage of ascites. However, he developed adult respiratory distress syndrome, worsening DIC, and renal dysfunction and died 2 months after admission. PMI showed infiltrative lung shadow, ascites, an abdominal aortic aneurysm, a wide infarction in the right parietal lobe, and multiple new cerebral infarctions. Autopsy examination showed purulent ascites, diffuse peritonitis, invasive bronchopulmonary aspergillosis, and non-bacterial thrombotic endocarditis that likely caused the cerebral infarctions.
A 65-year-old man with an old pontine infarction presented with a fever and neutropenia. Despite appropriate treatment, his fever persisted. CT showed bilateral upper lobe pneumonia, pain appeared in both femoral regions, and intramuscular abscesses of both shoulders developed. His pneumonia worsened, his level of consciousness decreased, right hemiplegia developed, and he died. PMI showed a newly diagnosed cerebral infarction in the left parietal lobe. The autopsy revealed bilateral bronchopneumonia, right-sided pleuritis with effusion, an intramuscular abscess in the right thigh, and fresh multiple organ infarctions. Systemic fibrin thrombosis and DIC were also found. Postmortem cultures showed E. coli and Burkholderia cepacia.
Cerebral infarction that is newly recognized on PMI might suggest the presence of severe systemic infection.
KeywordsCase report Postmortem imaging Cerebral infarction Infection Cause of death Autopsy Pathology
Cadavers can be evaluated using diagnostic imaging, which comprises one aspect of medical assessment at the time of death. Imaging of cadavers has also been referred to as postmortem imaging (PMI). However, this procedure is variously described as virtopsy in Switzerland , virtual autopsy in France , radio-autopsy in Germany , and autopsy imaging (Ai) in Japan . Although the descriptions and concept of PMI in these countries differ somewhat, all involve analysis of a cadaver by computed tomography (CT) and/or magnetic resonance imaging (MRI) to acquire postmortem medical information.
PMI is a useful diagnostic tool for a forensic case  that has no antemortem medical information. However, PMI is often performed in hospital deaths. On the other hand, the rate of the hospital autopsies has been decreasing worldwide in recent years, because the hospital autopsy requires consent in most countries. Furthermore, the brain examination rate of the hospital autopsy is only 20% at our hospital, because another consent is required for the brain examination. Therefore, PMI that can examine the intracerebral state of the cadaver is useful. The findings of PMI are interpreted by taking into consideration the postmortem changes based on the findings of imaging of the living body. Characteristic interpretations of the findings of PMI have yet to be developed.
In this paper, three cases of cerebral infarctions that were not found during life but were newly recognized on PMI are reported. The autopsies revealed severe systemic infectious diseases in all three cases. The aim of this paper is to suggest the possibility of the presence of a severe systemic infection when cerebral infarction is newly recognized on PMI.
An 81-year-old woman visited a hospital for a pacemaker check. At that time, slightly impaired liver function was noted. She then developed a fever of 38 °C. Although careful examinations to identify the cause of the fever were performed, the source could not be identified. Various cultures were also negative. Although antibiotic treatment was given, her fever and general status did not improve, and she was admitted to our hospital. On physical examination at admission, her temperature was 38 °C, blood pressure was 140/87 mmHg, and her pulse was 76/min. On blood tests, hemoglobin (Hb) was 11.8 g/dl, C-reactive protein (CRP) was 5.54 mg/dl, soluble interleukin-2 receptor (sIL-2R) was 3732 U/ml (standard 144–518 U/ml), and a tendency to disseminated intravascular coagulation (DIC) (PLT 5.4 x 104/μl, FDP 156 μg/ml, D-dimer 80 μg/ml) was seen. Slightly impaired liver function (aspartate aminotransferase (AST) 120 IU/l, alanine aminotransferase (ALT) 81 IU/l) was also found.
The chest CT on the second day after hospitalization showed a diffuse ground glass shadow and suspected interstitial pneumonia. On the fifth day after admission, contrast-enhanced CT showed a low-density area (LDA) in the left iliopsoas muscle, suggesting an iliopsoas muscle abscess. Staphylococcus aureus, Escherichia coli (E. coli), or tuberculosis was considered as the causative organism of the iliopsoas muscle abscess. Various dysfunctions, such as interstitial pneumonitis, liver damage, and DIC, were also present simultaneously. We assumed that there was a solitary underlying disease that could explain her clinical picture, for example, hematological disease, and treatment was started.
Since intense accumulation of fluoro-deoxy-glucose (FDG) was observed in bilateral lung fields on FDG-positron-emission tomography (PET), an inflammatory disorder, especially tuberculosis was suspected, and three-agent combined therapy was started on the 8th day after admission. However, neither the fever nor her general status improved, and the ground glass appearance had deteriorated further on the chest CT on the 16th day after admission.
On the 22nd day after admission (9 days before death), the patient’s respiratory condition deteriorated suddenly, and methylprednisolone pulse therapy resulted in no improvement. She died on the 32nd day after hospitalization. PMI and an autopsy (only thoracoabdominal) were performed 14 h after death (Additional file 1).
A 74-year-old man was taking a steroid (30 mg/day of predonin) for systemic lupus erythematosus (SLE) and was being followed in the outpatient department. A blood test showed severe anemia (Hb 3.8 g/dl), and he was hospitalized 2 months before death. Melena was found, but no bleeding source was identified even on gastroscopy and colonoscopy. Then, 14 days after admission, free air was found at the subphrenic region on chest X-ray and CT, and intestinal perforation was suspected. The patient was given a course of antibiotic treatment and drainage of ascites because of his general status.
The patient’s manifestations were relieved, but the inflammatory response increased again, and his respiratory condition suddenly worsened, requiring intensive care unit (ICU) admission. The onset of ARDS was suspected. He had DIC on admission, and it was exacerbated with progression of the infection. His inflammatory response, renal failure, and respiratory condition deteriorated, and he died 2 months after admission. PMI and an autopsy (only thoracoabdominal) were performed 2 h after death (Additional file 2).
A 65-year-old man developed a left pontine infarction 2 months before hospitalization. He had a fever of about 39 °C. Blood tests showed white blood cells of 300/μl (3% neutrophils; neutropenia), and he was hospitalized in the Department of Hematology. Drug-induced neutropenia was suspected, and granulocyte colony-stimulating factor and antibiotics were administered with stopping of oral medicine. However, his fever remained, and pneumonia of both upper lobes was diagnosed by CT on the fourth day after admission, and an antifungal drug was added. Pain in both femoral regions then appeared. His pneumonia got worse, and intramuscular abscesses of both shoulders were noted 30 days before death. Though an antimicrobial drug was added, the pneumonia worsened, and an inflammatory pleural effusion developed. The patient’s level of consciousness decreased, and complete paralysis of the right side arm and leg appeared. He died 3 days after his consciousness level decreased and the right hemiplegia developed. PMI and autopsy were performed 2 h after death (Additional file 3).
As described above, both cases 1 and 2 did not show neurological manifestations of the cerebral infarctions during their lifetime, and there were no findings on brain CT at the final antemortem imaging. However, in both cases, cerebral infarctions were recognized on the postmortem brain CT. In case 3, neurologic symptoms appeared in the agonal stage, and cerebral infarction was newly recognized on postmortem brain CT. The autopsy revealed severe infectious diseases in all three cases.
From October 2010 to January 2014, there were 106 cases that underwent both PMI and autopsy at the University of Fukui Hospital. PMI was performed at the Ai center of the University of Fukui with an 8-slice multi-detector CT scanner (Hitachi Medico, Tokyo, Japan) used exclusively for autopsies, as described previously . The corpus was placed in the supine position, and a full-body scan from the vertex to the toes was performed. The scanning conditions were 120 kV, 250 mA, 8 × 2.5 collimation, 1.125 pitch, 0.8-s rotation time, 5-mm slice thickness, and 5-mm increments [7, 8]. No contrast reagent was used in these cases.
In three of 106 cases (2.8%), cerebral infarction was newly recognized on PMI, and severe infection was diagnosed on the subsequent autopsy. However, this rate is limited to our hospital, which is a limitation of this report. Many of the autopsied subjects may have had an increased frequency of severe infectious diseases such as ARDS, sepsis, and pneumonia. However, our recent autopsy-based study of histiocytic hyperplasia with hemophagocytosis (polyhemophagocytosis)  showed that the incidence of polyhemophagocytosis was equal to that shown in the German, US, and Japanese literature [9–11], suggesting that the characteristics of our autopsied subjects were not biased. Therefore, there might be such cases in other hospitals. However, the exact frequency of cerebral infarction being newly recognized on PMI and severe infection being diagnosed on autopsy is not known.
Some comparison studies of PMI findings and pathological diagnosis by autopsy have been done. In two UK centers in Manchester and Oxford, 182 unselected cases were assessed by radiology (CT and MRI) and autopsy for the cause of death . In Aachen University Hospital, 29 cases were analyzed by CT and autopsy , and in the ICUs of Hamburg, 47 cases were analyzed by autopsy and PMI . However, none of these reported cases similar to the ones presented here.
The reported case of a woman in her 40s with familial hypercholesterolemia is similar . She underwent aortic valve replacement and coronary bypass surgery for aortic stenosis and stenosis of the left main coronary artery. However, she developed acute myocardial infarction and died of postoperative mediastinitis and multiple organ failure. PMI and autopsy were done. An LDA was found in the right parietal lobe on PMI. The autopsy revealed that she had disseminated cryptococcosis and developed multiple organ failure due to sepsis.
In the present three cases and the one case in the literature, the systemic infectious disease had already been known before death. However, if the cerebral infarction is newly found on PMI even if infection is not suspected or adequate testing is not possible before the death, systemic infectious diseases might be suspected.
The cause of cerebral infarction in all cases was considered to be a thrombus of thrombotic endocarditis or DIC due to the severe infection. In fact, some studies reported the association of cerebral infarction with prior infection and inflammatory processes [16–20]. However, no article has referred to the relationship between cerebral infarction in PMI and systemic infection. Thus, we would like to emphasize that findings of brain infarctions on PMI might imply systemic infection.
The rate of hospital autopsies has been decreasing worldwide in recent years. For example, autopsies are performed in less than 10% of all U.S. deaths . In the United Kingdom, the mean hospital autopsy rate in 2013 was 0.69% of hospital deaths . In Japan, according to the Japan Council for Quality Health Care, the autopsy rate in 2012 was 4.0%. To make matters worse, another consent is required for the brain examination, so the rate of brain examination at autopsy is still lower; it is only about 20% at our hospital. Therefore, the finding of brain infarction on PMI of the cadaver is important because it suggests the presence of systemic infection.
Systemic infection such as miliary tuberculosis is regarded as a disease for which diagnosis is difficult on PMI at present. However, there is a possibility that systemic infection might become a disease for which a diagnosis can be suspected on PMI based on an accumulation of cases similar to those presented here. Thus, we believe that we can improve the certainty of PMI by comparative examinations between PMI and autopsy findings.
Three cases with systemic infectious disease were presented in this report. All of them showed newly recognized cerebral infarctions on PMI. Cerebral infarction that is newly recognized on PMI might suggest the presence of severe systemic infection.
Adult respiratory distress syndrome
Disseminated intravascular coagulation
- E. coli :
Low density area
Middle cerebral artery
Magnetic resonance imaging
Soluble interleukin-2 receptor
Systemic lupus erythematosus
This report was partially supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan to S. Noriki (MEXT/JSPS KAKENHI Grant Number 26108009 and 26670348).
Availability of date and materials
All relevant data are within the paper. To protect the privacy of our patients, their full transcripts are not openly available. Information about the data and conditions for access are available from the corresponding author (Dr. Sakon Noriki, email@example.com).
SN was involved in the overall supervision and drafted the manuscript. KK, TS, and HK interpreted the PMI of all patients. SN, KI, and HN autopsied the patients and diagnosed the pathological findings. TY participated in the management of the patients of Cases 1 and 3. MI participated in the management of the patient of Case 2. All authors read and approved the final manuscript.
SN: MD, PhD, Associate Professor, Division of Tumor Pathology, Department of Pathological Sciences, School of Medical Sciences, University of Fukui, Fukui, Japan 23-3 Shimoaizuki, Matsuoka, Eiheiji, Fukui 910-1193, Japan.
KK: MBBS, Junior Associate Professor of Radiology, School of Medical Sciences, University of Fukui. TS: MD, PhD, Associate Professor of Radiology, School of Medical Sciences, University of Fukui. KI: MD, PhD, Junior Associate Professor of Molecular Pathology, School of Medical Sciences, University of Fukui. HK: MD, PhD, Professor of Radiology, School of Medical Sciences, University of Fukui. TY: MD, PhD, Professor of Hematology and Oncology, School of Medical Sciences, University of Fukui. MI: MD, PhD, Professor of Nephrology, School of Medical Sciences, University of Fukui. HN: MD, PhD, Professor of Molecular Pathology, School of Medical Sciences, University of Fukui.
The author(s) declare that they have no competing interests.
Consent for publication
Written, informed consent for publication of this case report and any accompanying images was obtained from the family of each deceased patient prior to autopsy.
Ethics approval and consent to participate
All research protocols were approved by the ethics review board of our institute and conformed to the provisions of the Declaration of Helsinki. The full name of the Ethics Committee that approved the study is“Research Ethics Committee, University of Fukui.”
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