Intracranial hemorrhage in dengue fever: management and outcome

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Surgical Neurology 72 (2009) 429 – 433 www.surgicalneurology-online.com

Infection

Intracranial hemorrhage in dengue fever: management and outcome A series of 5 cases and review of literature Rajinder Kumar, MBBS MS Mch⁎, Om Prakash, MBBS MS Mch, B.S. Sharma, MBBS MS Mch Department of Neurosurgery, All India Institute of Medical Sciences New Delhi, 110029 India Received 18 October 2008; accepted 20 January 2009

Abstract

Background: Dengue is one of the most important mosquito-transmitted arboviral diseases of tropical and subtropical parts of the world. It is estimated that 100 million cases occur per year, and 2.5 billion people at risk. Hemorrhagic complications causing encephalopathy is a rare but fatal. We discuss the management of 5 uncommon cases of intracranial hemorrhage in dengue. High index of suspicion is required for early diagnosis. Methods: Five of these patients with intracranial bleed were managed in neurosurgery unit. All the patients had deranged prothrombin time and thrombocytopenia. They were given platelet concentrates for correction of thrombocytopenia. All parameters and neurologic status were closely followed. Four of these patients had deterioration in neurologic status; 2 of them underwent surgery. Results: Two patients who underwent surgery had excellent outcome. One patient was managed conservatively with cerebral decongestants. Two patients with deep-seated bleed had very rapid deterioration and died. Conclusion: High index of suspicion in dengue is required especially during convalescence in those patients who are disoriented and have altered sensorium. It should not be misinterpreted as fever delirium or toxic encephalopathy. It needs immediate attention and investigation. Timely diagnosis and intervention can thus save many precious lives. © 2009 Elsevier Inc. All rights reserved.

Keywords:

Dengue fever; Encephalopathy; Dengue hemorrhagic fever; Dengue hemorrhagic shock syndrome

1. Introduction Dengue is a mosquito-borne infection transmitted to humans by Aedes aegypti (rarely A albopictus) and caused by one of the 4 closely related virus serotypes of the genus Flavivirus, family Flaviviridae. The global prevalence of dengue has grown dramatically in recent decades. This is endemic in different parts of the world. Dengue

Abbreviations: DHF, dengue hemorrhagic fever; DHSS, dengue hemorrhagic shock syndrome; CNS, central nervous system; WHO, world health organization; PT, prothrombin time; ALT, alanine transferase; NCCT, noncontrast computed tomography. ⁎ Corresponding author. Tel.: +91 09891353682; fax: +91 11 26588663. E-mail addresses: [email protected] (R. Kumar), [email protected] (B.S. Sharma). 0090-3019/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.surneu.2009.01.021

fever and DHF are acute febrile diseases, found in the tropics, with a geographic distribution similar to malaria [27]. Encephalopathy is a rare but fatal complication of dengue virus infection. The treatment of DHF with CNS involvement is supportive and symptomatic and rarely needs surgical intervention [5,20,30,31]. We report this uncommon complication of dengue in a series of 5 patients admitted in a single hospital and discuss their management and outcome.

2. Case reports We present a series of 5 cases of dengue hemorrhagic fever with intracranial bleed in a recent outbreak of dengue in Delhi from a single hospital (Table 1) (Figs. 1-5).

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Table 1 Case No

Age/sex

Presentation

Platelet count/ mL/PT

Dengue serology/type

CT scan finding

Neurologic deterioration on

Management

Outcome

1

22/male

Conservative

Died

5th day

Conservative

Improved

3

9/male

Left basal ganglia hematoma (Fig. 1) Right basal ganglia hematoma (Fig. 2) Left frontotemporal acute subdural hematoma (Fig. 3)

5th day

15/male

39 000 PT prolonged 19 000 PT prolonged 26 000 PT prolonged

Positive/type 2

2

7th day

Operated (craniotomy and evacuation of hematoma)

Improved

4

40/male

5

45/female

Fever, headache, myalgia Fever, headache, hemiparesis Fever, headache, vomiting, Unconscious E1VTM2 Fever, headache, vomiting, Unconscious E2 V4M6 Fever, headache, vomiting, unconscious

Positive/type 2 Positive/type 2

70 000 PT prolonged

Positive/type 2

Right frontoparietal acute subdural hematoma (Fig. 4)

5th day

Operated (craniotomy and hematoma evacuation and decompressive craniotomy)

Improved

15 000 PT prolonged

Positive/type 2

Left basal ganglia hematoma (Fig. 5)

15th day

Conservative

Died

We made a few interesting observations in our series. All these patients were perfectly healthy without any predisposing factor for intracranial bleed before this episode of illness. All of them had typical clinical presentations, prolonged PT, and severe thrombocytopenia. All were confirmed by serology. All of these patients were young adults, and most of them had intracranial bleed around convalescence (1 week after the onset of fever). All patients had moderate to severe headache before neurologic deterioration. It was interesting

to note that none of these patients had bleeding from other sites except intracranial bleed. All the patients were given platelet concentrate transfusions to keep platelet count above 100 000/mL. Two of these patients underwent surgery after the correction of PT and platelet counts. Both of these patients made good recovery. Three of them had deep-seated parenchymal hematoma, 1 had large temporal subdural hematoma, and 1 had multiple frontotemporal subdural hematoma. Urgent and timely operative intervention in

Fig. 1. (NCCT, head) Left basal ganglia bleed with intraventricular extension.

Fig. 2. (NCCT, head) Right basal ganglia hematoma.

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cases 3 and 4 led to good recovery in spite of poor neurologic status before surgery, whereas case 2 improved after cerebral decongestants. 3. Discussion

Fig. 3. (NCCT, head) Left frontotemporal acute subdural hematoma with midline shift.

Fig. 4. (NCCT, head) Multiple acute frontoparietal subdural hematoma.

Dengue is a mosquito-borne infection caused by arbovirus. This disease is caused by any one of the 4 types of viruses: dengue 1, 2, 3, and 4. People can be infected by one or more types during one episode of illness but only once by the same type in life time. Although dengue 1 causes high fever and joint pains, dengue 2 causes hemorrhagic fever resulting in spontaneous bleeding from skin and gums. Dengue 3 causes high fever, while dengue 4 causes DHF with shock. Each serotype is different from each other, and there is no cross-protection. Epidemics can be caused by multiple serotypes [23,26,29,31]. It is estimated that every year, there are 100 million cases of dengue fever and 2.5 billion people at risk. Dengue is the second most important mosquito-borne disease affecting humans after malaria [15,27]. There tend to remain large numbers of susceptible people in the population despite previous outbreaks because there are 4 different strains of the dengue virus [14,18,22]. Dengue fever is endemic in some parts of India [6-9]. There are increases in dengue cases after the monsoon (rainy season), when the conditions are ideal for mosquito breeding, that is, hot and humid environment with water pooling. Primary prevention of dengue mainly resides

Fig. 5. (NCCT, head) Left basal ganglia bleed with midline shift.

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in eliminating or reducing the mosquito vector for dengue [4,15,31]. The diagnosis of dengue is usually made clinically. According to WHO definition, dengue hemorrhagic fever is diagnosed when all the 4 criteria are fulfilled. These are fever, hemorrhagic tendencies (positive tourniquet test, spontaneous bruising, bleeding from mucosa, gingiva, hematemesis, bleeding from injection sites, etc), thrombocytopenia (b100 000 platelets/mm3 or estimated as b3 platelets per high-power field), and evidence of plasma leakage (hematocrit N20% higher than expected or drop in hematocrit of 20% or more from baseline after intravenous fluid administration) [25,31]. Although the common complications of dengue fever are fatigue and tiredness, dengue hemorrhagic fever is most dangerous of all. This can lead to bleeding and shock. The incidence of CNS involvement in dengue infection is low and ranges from 0.88% to 5.4%; the fatality rate is high. This encephalopathy may occur as a consequence of microcapillary hemorrhage leading to intracranial bleed, cerebral edema, hyponatremia, cerebral anoxia, and release of toxic products. Cardiac disturbances and reactive hepatitis have been reported during recent years [2,3,11,10,16,17]. The mainstay of treatment is supportive therapy. Platelet transfusion is rarely indicated unless the platelet level drops significantly or if there is significant bleeding. However, the transfusion is recommended on platelet count falling below 20 000 even without hemorrhage or approximately 50 000 with hemorrhage. Surgical intervention for ocular and intracranial surgeries can be undertaken after correction of coagulation defect with platelet count above 100 000/mL [1,19,21,31]. It seems important to note that these cases do not correspond to typical forms of hemorrhagic dengue because no other hemorrhages were observed in these patients. This observation of isolated intracranial bleed has not been described in literature. The most common hemorrhagic tendencies described in the literature are petechial hemorrhage, echymosis, gastrointestinal bleed, epistaxis, and others, which were conspicuously absent in our cases [12,13,26]. This raises the concern whether the CNS is more prone to bleed than other sites. Altered sensorium in these patients may be wrongly attributed to shock, delirium, and fever. Any delay in diagnosis of intracranial bleed in these patients may be fatal. Urgent and timely operative intervention in cases 3 and 4 led to good recovery in spite of poor neurologic status before surgery, whereas case 2 improved with cerebral decongestants. The exact mechanism of bleeding in DHF is not clear, but it seems to be multifactorial. Thrombocytopenia, prolonged prothrombin time, mild degree of disseminated intravascular coagulation, and hepatic dysfunction all seem to contribute synergistically. Shivbalan et al [24] have observed that the spontaneous bleed was most commonly associated with deranged prothrombin time. A combination of (a) biphasic pattern of fever, (b) hemoconcentration, (c) platelet count

less than 50 000/mm3, and (d) elevated ALT had a sensitivity of 79.2%, specificity of 64.7% with a positive predictive value of 70%, and a negative predictive value of 75% in predicting spontaneous bleeding in dengue [3,16,17,28]. Tripathi et al [28] observed hemorrhage in 2.5% of cases in their series. This included complications such as hematemesis (28%); epistaxis (27%); malena (14%); lymphadenopathy, especially cervical (31%); palatal rashes (27%); and hepatomegaly (24%); but none had intracranial bleed. None of the patients in our series had such findings except major intracranial bleed. The reason for this fatal intracranial bleed in the absence of bleed from the other sites commonly described in literature is not known. This change in trends needs further careful observation and investigation. 4. Conclusion A high degree of suspicion in dengue is required especially during convalescence in those patients who are disoriented and have altered sensorium. It should not be misinterpreted as fever delirium or toxic encephalopathy. It needs immediate attention and investigation. Timely diagnosis and intervention can thus save many precious lives. References [1] Ali N, Usman M, Syed N, Khurshid M. Haemorrhagic manifestations and utility of haematological parameters in dengue fever. A tertiary care centre experience at Karachi. Scand J Infect Dis 2007:1-4. [2] Angibaud G, Luaute J, Laille M. Brain involvement in dengue fever. J Clin Neurosci 2001;8:63-5. [3] Attavinijtrakarn P. Hepatic dysfunction in dengue haemorrhagic fever in Paholpolpayuhasaena Hospital. Thai J Pediatr 2000;39:265-76. [4] Centers for Disease Control and Prevention. Imported dengue— Florida, 1997-1998. Can Commun Dis Rep 2000;26(9):77-9. [5] Chye JK, Lim CT, Ng KB. Vertical transmission of dengue. Clin Infect Dis 1997;25(6):1374-7. [6] Dar L, Broor S, Sengupta S, Xess I, Seth P. The first major outbreak of dengue hemorrhagic fever in Delhi, India. Emerg Infect Dis 1999;5: 589-90. [7] Dar L, Gupta E, Narang P, Broor S. Co-circulation of dengue serotypes 1, 2, 3 and 4 during the 2003 outbreak in Delhi, India. Emerg Infect Dis 2006;12:352-3. [8] Dash PK, Parida MM, Saxena P, Abhyankar A, Singh CP, Tewari KN, Jana AM, Lakshman Rao PV. Reemergence of dengue virus type -3 (subtype III) in India: implications for increased incidence of DHF and DSS. Virol J 2006;3:55. [9] Dash PK, Saxena P, Abhyankar A, Bhargava R, Jana AM. Emergence of dengue virus type-3 in northern India. Southeast Asian J Trop Med Public Health 2005. [10] Diaz A, Kouri G, Guzman MG. Description of the clinical picture of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) in adults. Bull Pan Am Health Organ 1988;22(2):133-44. [11] Gubler DJ. Dengue and dengue hemorrhagic fever. Clin Microbiol Rev 1998;11(3):480-96. [12] Gupta E, Dar L, Kapoor G, Broor S. The changing epidemiology of dengue in Delhi, India. Virology Journal 2006;3:92. [13] Gupta E, Dar L, Narang P, Srivastava VK, Broor S. Serodiagnosis of dengue during an outbreak at a tertiary care hospital in Delhi. Indian J Med Res 2005;121:36-8.

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Commentary The initial clinical report of dengue has been attributed to Benjamin Rush in 1780. Over the ensuing years, innumerable epidemics have occurred worldwide. Severe dengue with hemorrhagic manifestations has occurred for more than 100 years and has increased during the past 25 years. Despite prior immunity, many individuals are able to generate binding but nonneutralizing antibody. Infection then results, in some individuals, in the release of cytokines with vasoactive or procoagulant properties, capillary leakage, disseminated intravascular coagulation, and bleeding that can be augmented by thrombocytopenia—a common hematologic complication of dengue. Kumar et al describe 5 cases of intracranial hemorrhage without any other evidence for bleeding. All patients were thrombocytopenic, had a prolonged prothrombin time, and manifested intravascular coagulation—common biologic findings in dengue. However, for the first time, hemorrhage was recorded only in the central nervous system. As the authors state, the reason for only an intracerebral bleed is not known but could be related to subtle underlying cerebrovascular disease. Further observations are needed to explain this unusual manifestation. Lawrence A. Cone, MD Eisenhower Medical Center Rancho Mirage, CA 92270, USA