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 ~  Abstract
 ~ Introduction
 ~ Case Report
 ~ Discussion
 ~  References
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  Table of Contents  
Year : 2013  |  Volume : 31  |  Issue : 1  |  Page : 79-81

First case report of acute hemorrhagic leukoencephalitis following Plasmodium vivax infection

1 Department of Radio diagnosis, JN Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
2 Department of Microbiology, JN Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India

Date of Submission12-Aug-2012
Date of Acceptance31-Oct-2012
Date of Web Publication15-Mar-2013

Correspondence Address:
V Venugopal
Department of Radio diagnosis, JN Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0255-0857.108736

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 ~ Abstract 

Acute hemorrhagic leukoencephalitis (AHLE, Hurst's disease) is a rare hyperacute variant of acute disseminated encephalomyelitis (ADEM) characterized by severe, rapidly progressive clinical illness and hemorrhagic necrosis of white matter. Like ADEM, it is often preceded by viral illness or vaccination. Plasmodium vivax infection is usually uncomplicated and non-fatal with only a handful of reports of central nervous system complications. In this article, we report a previously unknown association between AHLE and P. vivax infection.

Keywords: Acute hemorrhagic, Infectious diseases, Leukoencephalitis, Malaria, Plasmodium vivax

How to cite this article:
Venugopal V, Haider M. First case report of acute hemorrhagic leukoencephalitis following Plasmodium vivax infection. Indian J Med Microbiol 2013;31:79-81

How to cite this URL:
Venugopal V, Haider M. First case report of acute hemorrhagic leukoencephalitis following Plasmodium vivax infection. Indian J Med Microbiol [serial online] 2013 [cited 2021 Mar 5];31:79-81. Available from:

 ~ Introduction Top

Acute hemorrhagic leukoencephalitis (AHLE) is a hyperacute encephalomyelitis characterized by hemorrhagic necrosis of white matter. A 22-year-old patient with high Plasmodium vivax parasitemia developed acute encephalopathy. AHLE was diagnosed based on clinico-imaging findings. To the best of our knowledge, this is the first reported case of AHLE linked to P. vivax.

 ~ Case Report Top

A previously healthy 22-year-old male patient was admitted to our hospital with one week history of fever, chills, and lethargy. On physical examination the patient had high grade fever of 40°C and mild hepatosplenomegaly. Routine blood investigations were performed. Thin and thick blood smear examinations revealed P. vivax trophozoites and schizonts with 3+ parasitemia (1-10 parasites/single thick field) [Figure 1]. Further testing with malaria pf/pv card (an immune-assay technique based on sandwich principle) showed positive control line and test line P. Test line F was negative confirming presence of non-falciparum malaria parasites in the patient's blood. Since the malarial parasites in North India are chloroquine resistant, the patient was started on Artesunate 120 mg iv stat followed by 60 mg iv for 5 days. The patient improved clinically over the next 3 days with remission of fever. Repeat Geimsa stained thin-smear examination revealed remission of parasitemia. Unexpectedly, 5 days after admission, the patient had recurrent attacks of convulsions. During the inter-ictal period, the patient was mildly disoriented and complained of diminution of vision on both sides. Over the next 2 days, the patient's neurological status worsened with intractable seizure episodes and onset of delirium. Magnetic Resonance imaging (MRI) examination of the patient revealed ill-defined asymmetrical hyperintense lesions on T2 and fluid-attenuated inversion-recovery (FLAIR) sequences, diffusely distributed in bilateral occipital and parietal regions. There were multiple hyperintense foci within these lesions on T1 sequences. On Gradient Echo (GRE), these foci showed "blooming," suggesting them to be hemorrhagic foci [Figure 2]a, b. There was no enhancement of the lesions in the post-contrast sequences. Cerebrospinal fluid analysis revealed marked pleocytosis with predominant neutrophils (white blood cell count of 1400 cells/mm 3 with 79% neutrophils and few red blood cells), increased protein level (120 mg/dL), and decreased glucose level (40 mg/dL). Gram stain and acid fast stain were negative. CSF culture studies were unyielding. The microbiological and polymerase chain reaction (PCR) analysis for viral nucleic acids (e.g., Herpes simplex, Japanese Encephalitis virus, enterovirus, adenovirus, varicella, measles, mumps, and arboviruses) in CSF were negative. Serology for HIV and syphilis were also negative. After reasonable exclusion of alternative infective or immunological explanations for the clinical presentation and characteristic imaging findings, a diagnosis of acute hemorrhagic leukoencephalitis due to P. vivax was made. When a decision of starting prednisolone therapy for the patient was made, during that period, unfortunately, his clinical condition worsened and the patient died on the tenth post admission day.
Figure 1: Thin fi lm micrograph reveals a mature Plasmodium vivax trophozoite showing amoeboid cytoplasm, large chromatin dot, and fine, yellowish-brown pigment

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Figure 2: (a) FLAIR sequence shows asymmetrical heterogeneous hyperintense lesions in bilateral periventricular regions. (b) GRE sequence shows "blooming" (i.e,. dark) foci suggestive of hemorrhage

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 ~ Discussion Top

P. vivax is geographically the most widely distributed human malaria, and the major cause of malaria outside Africa. An estimated 80-300 million clinical cases occur every year with up to 2.5 billion people at risk. [1] P. vivax malaria usually presents with repeated episodes of high fever preceded by violent headache, chills, and profuse sweating often accompanied by vomiting, diarrhea, and enlargement of the spleen. Infection by P. vivax unlike that by P. falciparum is typically an uncomplicated disease and is rarely fatal. The weaker host response at lower parasitemia levels, synergy between inflammatory cytokines, and hypoxia due to inducible NO synthase (iNOS) induction, lower tumor necrosis factor (TNF-alpha)/parasitemia, and Human neutrophil elastase (HNE)/parasitemia ratios in P. falciparum than in P. vivax malaria are the proposed reasons for the differences in the pathology observed among them. [2],[3] Occasionally, P. vivax can also follow a severe course similar to P. falciparum causing cerebral malaria and other complications. The main hypothesis behind causation of cerebral malaria involves sequestration of erythrocytes infected with P. falciparum trophozoites, and schizonts in cerebral capillaries and postcapillary venules.

Acute disseminated encephalomyelitis (ADEM) is a monophasic inflammatory demyelinating disease affecting predominantly children or young adults and characterized by multifocal neurologic deficits of rapid onset. Unlike infectious encephalitis due to direct invasion of the organisms into the brain, ADEM is believed to be a post-infectious encephalitis resulting from a transient autoimmune response towards myelin-oligodendrocyte antigens possibly via molecular mimicry or by non-specific activation of autoreactive T cell clones. [4] Acute hemorrhagic leukoencephalitis (AHLE) is considered to be a hyperacute form of ADEM. AHLE and ADEM share many features and may be part of a spectrum of disease with the same fundamental process rather than distinct entities. A similar study reported the association of P. vivax infection with acute necrotizing encephalopathy. [5] The hallmarks of this encephalopathy are multifocal symmetric brain lesions affecting the bilateral thalami and/or cerebral periventicualr white matter, brainstem tegmentum, or cerebral medulla.

One important clinical consideration in patients with neurological symptoms after Plasmodium infections is cerebral malaria. A strict definition of cerebral malaria has been recommended by WHO for the sake of clarity, and this requires the presence of unarousable coma, exclusion of other encephalopathies, and confirmation of P. falciparum infection. [6] Since none of these features were present in our patient, cerebral malaria was excluded. For the MR imaging findings noted in our case, close mimickers were the fulminant variants of multiple sclerosis, infectious encephalitis, and ADEM. Multiple sclerosis is usually a polyphasic disease characterised by disease dissemination in space and time. Even its fulminant rapidly progressive variants such as Marburg's and Schilder's diseases usually do not have high fever or CSF pleocytosis. Moreover, hemorrhagic foci are not usually seen in multiple sclerosis. [7] Absence of any clinical and laboratory evidence for viral or fungal infections rules out infectious encephalitis. [8] As discussed earlier, the more rapid and severe clinical course, presence of polymorphonuclear pleocytosis rather than lymphocytic pleocytosis, and the presence of hemorrhagic foci within the lesions were clear differentiating points of AHLE from ADEM. [9]

By excluding other reasonable explanations, we arrived at a clinical diagnosis of acute hemorrhagic leukoencephalitis in our patient on the basis of typical clinical course, CSF analysis, and characteristic imaging findings. The temporal association of P. vivax infection with absence of evidence for any other infections strongly suggests its possible etiological role. Even though an association between P. vivax and ADEM had been reported previously in a Japanese man, [10] this is the first case where its association with acute hemorrhagic leukoencephalitis is being reported. Further research is needed to establish a clear casual association.

 ~ References Top

1.Mueller I, Galinski MR, Baird JK, Carlton JM, Kochar DK, Alonso PL, et al. Key gaps in the knowledge of Plasmodium vivax, a neglected human malaria parasite. Lancet Infect Dis 2009;9:555-66.  Back to cited text no. 1
2.Clark IA, Cowden WB. Why is the pathology of falciparum worse than that of vivax malaria? Parasitol Today 1999;15:458-61.  Back to cited text no. 2
3.Hemmer CJ, Holst FG, Kern P, Chiwakata CB, Dietrich M, Reisinger EC. Stronger host response per parasitized erythrocyte in Plasmodium vivax or ovale than in Plasmodium falciparum malaria. Trop Med Int Health 2006;11:817-23.  Back to cited text no. 3
4.Tselis AC, Lisak RP. Acute disseminated encephalomyelitis and isolated central nervous system demyelinative syndromes. Curr Opin Neurol 1995;8:227-9.  Back to cited text no. 4
5.Yadav S, Das CJ, Kumar V, Lodha R. Acute necrotizing encephalopathy. Indian J Pediatr 2010;77:307-9.  Back to cited text no. 5
6.Kuperan S, Ostrow P, Landi MK, Bakshi R. Acute hemorrhagic leukoencephalitis vs ADEM: FLAIR MRI and neuropathology findings. Neurology 2003;60:721-2.  Back to cited text no. 6
7.Niebler G, Harris T, Davis T, Roos K. Fulminant multiple sclerosis. AJNR Am J Neuroradiol 1992;13:1547-51.  Back to cited text no. 7
8.An SF, Groves M, Martinian L, Kuo LT, Scaravilli F. Detection of infectious agents in brain of patients with acute hemorrhagic leukoencephalitis. J Neurovirol 2002;8:439-46.  Back to cited text no. 8
9.Trampuz A, Jereb M, Muzlovic I, Prabhu RM. Clinical review: Severe malaria. Crit Care 2003;7:315-23.  Back to cited text no. 9
10.Koibuchi T, Nakamura T, Miura T, Endo T, Nakamura H, Takahashi T, et al. Acute disseminated encephalomyelitis following Plasmodium vivax malaria. J Infect Chemother 2003;9:254-6.  Back to cited text no. 10


  [Figure 1], [Figure 2]

This article has been cited by
1 First case of acute haemorrhagic leucoencephalitis following Plasmodium vivax infection: Comment
Shanbag, P.
Indian Journal of Medical Microbiology. 2013; 31(4): 422


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