Forensic Sci Med Pathol DOI 10.1007/s12024-014-9535-x
IMAGES IN FORENSICS
The pathological features of Wernicke encephalopathy Kelly Olds • Neil E. I. Langlois • Peter Blumbergs Roger W. Byard
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Accepted: 9 January 2014 Ó Springer Science+Business Media New York 2014
Case report A 47-year-old man with a history of alcoholic liver disease was found dead at his home address on the floor, lying face down. He had been unwell for 2 months prior to death and had complained of abdominal pain. He also had a diagnosis of prolonged QT interval. At autopsy there was no evidence of liver failure although the liver was fatty and fibrotic. There was a congenital anomaly of the coronary arteries with the circumflex coronary artery arising from the right sinus of Valsalva with significant narrowing of the ostium. There was no evidence of trauma and toxicological screening of blood was unremarkable. Biochemical analysis of vitreous humor revealed elevated sodium (144 mmol/L) and creatinine (217 lmol/L) levels in keeping with terminal dehydration and renal failure, with a normal b-hydroxy butyrate (thus excluding alcoholic ketoacidosis). Although the brain appeared externally unremarkable with no vermal atrophy of the cerebellum, sectioning of the mammillary bodies demonstrated symmetrical hemorrhage highly suggestive of Wernicke encephalopathy (Figs. 1, 2). Focal hemorrhagic areas were also noted within the walls of the third ventricle.
K. Olds N. E. I. Langlois R. W. Byard School of Medical Sciences, The University of Adelaide, Frome Road, Adelaide, SA 5005, Australia N. E. I. Langlois P. Blumbergs R. W. Byard Forensic Science SA, Adelaide, SA 5005, Australia R. W. Byard (&) Discipline of Anatomy and Pathology, Level 3 Medical School North Building, The University of Adelaide, Frome Road, Adelaide, SA 5005, Australia e-mail:
[email protected]
Microscopically the mammillary bodies displayed recent microhemorrhages and prominent microvascular proliferation with endothelial swelling typical of Wernicke encephalopathy (Fig. 3). The mammillothalamic tracts and the walls of third ventricle also contained microhemorrhages. There was patchy microvacuolation of the neuropil with unremarkable neurons, fibrous astrocytes, and occasional perivascular macrophages containing hemosiderin, indicative of more chronic disease. Mild extravasation of erythrocytes and prominent congested vessels were noted within medullary dorsal motor vagal nuclei. Death was attributed to natural causes, most likely involving a combination of cardiac and alcohol-related disease. The striking finding was of clinically unsuspected Wernicke encephalopathy.
Discussion Wernicke encephalopathy is a neurological disorder resulting from thiamine (vitamin B-1) deficiency [1]. Although in Western countries it occurs predominantly in alcoholics, related to poor dietary intake and impaired utilization, it can also be caused by a variety of other conditions that interfere with normal thiamine metabolism. These include starvation, bariatric surgery, hyperemesis gravidarum, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), and in infants given thiamine-deficient formulas [1, 2]. The clinical prevalence of Wernicke encephalopathy is uncertain as autopsy studies indicate that the condition is likely under-diagnosed during life [3]. Delay in diagnosis may result from nonspecific symptoms that resemble intoxication. The symptoms, severity, and the regions of the brain that are affected are also variable due to a
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Fig. 1 Coronal section of the brain at the level of the mammillary bodies demonstrating symmetrical hemorrhage highly suggestive of Wernicke encephalopathy
Fig. 2 Higher power view of the mammillary bodies (arrow) showing interstitial hemorrhage
combination of genetic and environmental factors [4]. The classic clinical triad of Wernicke encephalopathy includes ophthalmoplegia, ataxia, and mental confusion [5]. The latter may manifest as full blown Korsakoff psychosis with delusions, hallucinations, and confabulation [4]. The three stages of Wernicke encephalopathy are acute, sub-acute, and chronic, however repeated episodes may result in acute-on-chronic features [6]. This was observed in the reported case which showed predominantly acute hemorrhagic changes, with more subtle chronic changes of fibrous astrocytes and perivascular hemosiderin-containing macrophages. Neuropathological features include petechial hemorrhages, with lesions of the mammillary bodies, the periventricular regions of third and fourth ventricles and the aqueduct [6]. Histological sections, as demonstrated in
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Fig. 3 Microscopic section of the mammillary bodies showing recent microhemorrhages and prominent microvascular proliferation with endothelial swelling typical of Wernicke encephalopathy (hematoxylin and eosin (H&E) 9100)
the reported case (Fig. 3), may show parenchymal rarefaction with macrophages, and prominent capillaries [4]. Another condition that may be found at autopsy in individuals with Wernicke encephalopathy is central pontine myelinolysis (CPM), a disease where demyelination occurs in the central areas of the base of the pons [7]. While Wernicke encephalopathy is not usually responsible for death, with a mortality of around 20 % [8], sudden death in alcoholics is a recognized occurrence, often with few postmortem findings [9]; it has been stated that ‘‘the relationship between alcohol and ventricular tachycardia as well as SCD [sudden cardiac death] is definite’’ [10]. Cardiac arrhythmias may be precipitated by either alcohol ingestion or its withdrawal. In the present case there was a history of prolonged QT interval and an anomalous circumflex coronary artery, both of which may have contributed to sudden death [11, 12]. Prolonged QT interval is yet another feature of alcoholism [10]. The normal bhydroxybutyrate level and absence of renal tubular epithelial cell vacuolation excluded alcoholic ketoacidosis [13]. As Wernicke encephalopathy is a potentially treatable and preventable disease, early diagnosis is extremely important in order to prevent permanent neurological damage and death [3]. However, the importance of careful postmortem examination in alcoholics is also emphasized, as 75–80 % of cases of Wernicke encephalopathy identified at autopsy have been found to be clinically occult [1].
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