Inflammation ( # 2013) DOI: 10.1007/s10753-013-9776-y
Role of Vascular Endothelial Growth Factor (VEGF) in the Neurological Manifestations of Dengue: A Preliminary Study Usha Kant Misra,1,2 Jayantee Kalita,1 and Avadhesh Pratap Singh1
Abstract—This study reports on vascular endothelial growth factor (VEGF) in dengue patients with neurological manifestations. Their bleeding diathesis, hypotension, edema, flushing, and hepatosplenomegaly were noted. Complete blood counts, serum chemistry, coagulation profile, liver and kidney function tests, creatine kinase (CK), and MRI in encephalopathic patients were carried out. Serum VEGF was estimated by ELISA in 21 dengue patients and 14 controls. Twelve patients had dengue fever (DF), eight dengue hemorrhagic fever (DHF), and one dengue shock syndrome (DSS). Fifteen patients had neurological manifestation, 12 had muscle involvement (raised CK with or without weakness), and 3 had encephalopathy. The VEGF level in dengue patients was 50.0±56.1 pg/mL and in the controls, 60.6± 20.3 pg/mL. The VEGF level neither correlated with the severity nor with the neurological involvement. Thrombocytopenia, however, correlated with the severity of dengue and neurological manifestations. The VEGF level is not related to the severity of dengue and neurological syndrome. KEY WORDS: dengue; VEGF; dengue hemorrhagic fever; dengue shock syndrome; encephalopathy; myopathy.
INTRODUCTION Dengue is one of the most important arboviral infections in humans. About 50–100 million dengue patients occur annually, and 2.5 billion people are at risk of developing dengue [1]. Dengue is prevalent in Asia, Africa, Australia, Americas, and southern Europe. The critical determinants of clinical manifestations in dengue are platelet dysfunction, coagulopathy, and capillary leakage. The resulting manifestations are dengue fever, dengue hemorrhage fever (DHF), and dengue shock syndrome (DSS). Vascular endothelial growth factor has been reported to be responsible for capillary leakage in dengue and has shown to express more frequently in dengue shock syndrome compared to dengue fever [2, 3]. The neurological manifestations in dengue are diverse and include encephalopathy, seizure, and transient muscle dysfunction [4–6]. The neurological manifestations of dengue may be due to 1
Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow 226014, India 2 To whom correspondence should be addressed at Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow 226014, India. E-mail: [email protected]; [email protected]
hypotension, hypovolemia, liver and kidney dysfunction, and intracerebral hemorrhage, but in some patients, primary encephalitis has been reported [6–8]. VEGF, however, is critical in the pathogenesis of dengue by producing change in vascular permeability, but its relationship with various neurological manifestations of dengue virus infection has not been evaluated. In this preliminary communication, we report on the role of VEGF in patients with dengue infection and compare it in the patients with and without neurological manifestations.
MATERIALS AND METHODS The patients with dengue virus infection admitted to neurology service during 2010 were prospectively evaluated. The diagnosis of dengue virus infection was based on the detection of NS1 antigen and/or anti-dengue IgM antibody in the serum. The patients were subjected to medical history including myalgia, weakness, skin rash, bleeding, headache, vomiting, fever, and edema. The clinical examination included pulse, blood pressure, pallor, edema, flushing, eye congestion, petechiae, ecchymosis, jaundice, lymphadenopathy, liver and spleen enlargement, ascites,
0360-3997/13/0000-0001/0 # 2013 Springer Science+Business Media New York
Misra, Kalita, and Singh and pleural effusion. The consciousness was assessed by the Glasgow Coma Scale (GCS). Presence of cranial nerve palsy was noted. The muscle tenderness, power, tone, reflex, sensations, and coordination were tested. Investigations. Blood counts, hemoglobin, hematocrit, platelet count, prothrombin time, activated partial thromboplastin time, blood sugar, blood urea nitrogen, serum creatinine, bilirubin, transaminase, lactic dehydrogenase, serum electrolyte, and creatine kinase (CK) were estimated. Electrocardiogram and radiograph of the chest were carried out. Serum VEGF was estimated by ELISA using an ELISA Kit (Genetix Biotech, India), and serum IgG and IgM against dengue virus were also estimated by ELISA using a Panbio (Australia). Statistical analysis. The VEGF level was correlated with serum IgM and IgG antibody as well as its level was compared with different subgroups of dengue (dengue fever, DHF, and DSS) and those with and without neurological involvement using various parametric and nonparametric tests. The other hematological and biochemical parameters were also compared with different subtypes of dengue and the patients with and without neurological
involvement. All these analyses were done in SPSS 16 version software, and the variable was considered significant if the two-tailed P value was
Role of Vascular Endothelial Growth Factor (VEGF) in the Neurological Manifestations of Dengue: A Preliminary Study Usha Kant Misra,1,2 Jayantee Kalita,1 and Avadhesh Pratap Singh1
Abstract—This study reports on vascular endothelial growth factor (VEGF) in dengue patients with neurological manifestations. Their bleeding diathesis, hypotension, edema, flushing, and hepatosplenomegaly were noted. Complete blood counts, serum chemistry, coagulation profile, liver and kidney function tests, creatine kinase (CK), and MRI in encephalopathic patients were carried out. Serum VEGF was estimated by ELISA in 21 dengue patients and 14 controls. Twelve patients had dengue fever (DF), eight dengue hemorrhagic fever (DHF), and one dengue shock syndrome (DSS). Fifteen patients had neurological manifestation, 12 had muscle involvement (raised CK with or without weakness), and 3 had encephalopathy. The VEGF level in dengue patients was 50.0±56.1 pg/mL and in the controls, 60.6± 20.3 pg/mL. The VEGF level neither correlated with the severity nor with the neurological involvement. Thrombocytopenia, however, correlated with the severity of dengue and neurological manifestations. The VEGF level is not related to the severity of dengue and neurological syndrome. KEY WORDS: dengue; VEGF; dengue hemorrhagic fever; dengue shock syndrome; encephalopathy; myopathy.
INTRODUCTION Dengue is one of the most important arboviral infections in humans. About 50–100 million dengue patients occur annually, and 2.5 billion people are at risk of developing dengue [1]. Dengue is prevalent in Asia, Africa, Australia, Americas, and southern Europe. The critical determinants of clinical manifestations in dengue are platelet dysfunction, coagulopathy, and capillary leakage. The resulting manifestations are dengue fever, dengue hemorrhage fever (DHF), and dengue shock syndrome (DSS). Vascular endothelial growth factor has been reported to be responsible for capillary leakage in dengue and has shown to express more frequently in dengue shock syndrome compared to dengue fever [2, 3]. The neurological manifestations in dengue are diverse and include encephalopathy, seizure, and transient muscle dysfunction [4–6]. The neurological manifestations of dengue may be due to 1
Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow 226014, India 2 To whom correspondence should be addressed at Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow 226014, India. E-mail: [email protected]; [email protected]
hypotension, hypovolemia, liver and kidney dysfunction, and intracerebral hemorrhage, but in some patients, primary encephalitis has been reported [6–8]. VEGF, however, is critical in the pathogenesis of dengue by producing change in vascular permeability, but its relationship with various neurological manifestations of dengue virus infection has not been evaluated. In this preliminary communication, we report on the role of VEGF in patients with dengue infection and compare it in the patients with and without neurological manifestations.
MATERIALS AND METHODS The patients with dengue virus infection admitted to neurology service during 2010 were prospectively evaluated. The diagnosis of dengue virus infection was based on the detection of NS1 antigen and/or anti-dengue IgM antibody in the serum. The patients were subjected to medical history including myalgia, weakness, skin rash, bleeding, headache, vomiting, fever, and edema. The clinical examination included pulse, blood pressure, pallor, edema, flushing, eye congestion, petechiae, ecchymosis, jaundice, lymphadenopathy, liver and spleen enlargement, ascites,
0360-3997/13/0000-0001/0 # 2013 Springer Science+Business Media New York
Misra, Kalita, and Singh and pleural effusion. The consciousness was assessed by the Glasgow Coma Scale (GCS). Presence of cranial nerve palsy was noted. The muscle tenderness, power, tone, reflex, sensations, and coordination were tested. Investigations. Blood counts, hemoglobin, hematocrit, platelet count, prothrombin time, activated partial thromboplastin time, blood sugar, blood urea nitrogen, serum creatinine, bilirubin, transaminase, lactic dehydrogenase, serum electrolyte, and creatine kinase (CK) were estimated. Electrocardiogram and radiograph of the chest were carried out. Serum VEGF was estimated by ELISA using an ELISA Kit (Genetix Biotech, India), and serum IgG and IgM against dengue virus were also estimated by ELISA using a Panbio (Australia). Statistical analysis. The VEGF level was correlated with serum IgM and IgG antibody as well as its level was compared with different subgroups of dengue (dengue fever, DHF, and DSS) and those with and without neurological involvement using various parametric and nonparametric tests. The other hematological and biochemical parameters were also compared with different subtypes of dengue and the patients with and without neurological
involvement. All these analyses were done in SPSS 16 version software, and the variable was considered significant if the two-tailed P value was
