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Year : 2007  |  Volume : 10  |  Issue : 1  |  Page : 49-51

An interesting case of hemiplegia in a child

1 Department of Neurology, Medical College, Thiruvananthapuram, Kerala, India
2 Department of Pathology, Medical College, Thiruvananthapuram, Kerala, India
3 Department of Cardiology, Medical College, Thiruvananthapuram, Kerala, India

Correspondence Address:
Sadanandavalli Retnaswami Chandra
Sarayu, Chirakkara Temple Lane, Kaimanam, Thiruvananthapuram, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0972-2327.31486

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Hemiplegia in children occurs due to several causes. We report an interesting case who presented with prolonged fever, native valve endocarditis and infection triggered Macrophage activation syndrome. Macrophage activation syndrome (Hemophagocytic Lymphohistiocytosis syndrome) is a rare, potentially fatal inflammatory response syndrome characterized by fever, pancytopenia, rash, falling ESR, increased ferritin, increased triglycerides and hypofibrinogenemia. Central nervous system involvement is frequent with, seizures, irritability, stiff neck, cranial nerve palsy, ataxia and coma.

Keywords: Childhood hemiplegia, hemophagocytic lymphohistiocytosis, macrophage activation syndrome, native valve endocarditis

How to cite this article:
Chandra SR, Syamlal S, Ravi K, Somarajan A, Suresh K. An interesting case of hemiplegia in a child. Ann Indian Acad Neurol 2007;10:49-51

How to cite this URL:
Chandra SR, Syamlal S, Ravi K, Somarajan A, Suresh K. An interesting case of hemiplegia in a child. Ann Indian Acad Neurol [serial online] 2007 [cited 2022 Dec 1];10:49-51. Available from:

   Introduction Top

Hemiplegia in children is different from that of adults in all respects - aetiopathology and prognosis.[1] Here we report a hemiplegic child who presented with pyrexia of unknown origin (PUO) in whom the evaluation revealed the diagnosis of native valve endocarditis with Macrophage Activation syndrome (Hemophagocytic Lymphohistiocytosis syndrome). It is a rare, potentially fatal[2] inflammatory response syndrome characterized by fever, pancytopenia, rash, falling erythrocyte sedimentation rate (ESR), increased ferritin, increased triglycerides and hypofibrinogenemia.[3] High degree of suspicion and early recognition is needed to save life.

   Case Report Top

A 12-year-old male child was admitted with the fever of one-year duration (PUO). He had been treated with repeated courses of antibiotics at several centers with transient improvement in fever. He was later put on empirical anti tuberculous treatment elsewhere with four drugs regime. While on treatment, he developed left hemiparesis, seizures and bilateral blindness, few days before admission to our department. At first admission to our hospital we presumed it to be infective vasculitis secondary to tuberculous meningitis.

General examination revealed a pale febrile child, who had very poor vision (6/60 right eye and 6/18 left eye). His pupils were sluggish and there was optic nerve head edema. Retina and macula were normal. He had left hemiparesis and a left focal seizure, in addition to hepatosplenomegaly. He was reassessed for PUO including vasculitis work-up [Table - 1]. He had massive splenomegaly, hepatomegaly ascites, pancytopenia and normal ESR Following investigations were negative. Anti Nuclear Antibody, Anti double stranded deoxy nucleic acid, P-Anti Neutrophil Cytoplasmic Antibody, C-Anti Neutrophil Cytoplasmic Antibody, Antiphospho Lipid Antibody, Widal, Blood culture (twice), Urine culture, Sputum AFB, cerebrospinal fluid (CSF) TB IgG/IgM  Brucella More Details antibody, RBS, Urea LFT, RFT Lipidogram and total protein. Mantoux test was negative. CT and MRI Brain were normal. CSF study showed 45 lymphocytes with normal glucose and protein.

Child received 2 gm methyl prednisolone followed by 16 mg methylprednisolone tapered over three weeks. He had reversal of all symptoms and signs in twelve days and he was continued on anti tuberculous treatment alone. Hemiparesis recovered over a period of two weeks. However he was readmitted with fever of two weeks, hepatosplenomegaly, irritability, rashes over trunk and upper thighs and with episodes of focal seizures. He was re-evaluated for fever and found to have features of native valve endocarditis with vegetations on the anterior mitral leaflet, in echocardiography [Figure - 1].

He underwent bone marrow examination, which showed a cellular marrow with reversed M/E ratio, erythroid hyperplasia with normoblastic maturation. Binucleate megaloblasts and cells in mitoses were seen. Myeloid series showed all stages of maturation with shift to left. Histiocytes with hemophagocytosis and few degraded cells. Megakaryocytes were found in very few clumps and some were hypolobulated [Figure - 2].

His S. Ferritin (605 mg/dl) and Triglycerides (322 mg/dL) were elevated. Fibrinogen was not done. ESR was normal. He was treated with Inj Vancomycin and Rifampicin, for two weeks and was evaluated with serial follow-up Echocardiograms. He was given intravenous immunoglobulin and methylprednisolone, with which his clinical, hematological and cardiac picture reversed and he was sent home happily. Repeat ultrasound showed reduction in hepatosplenomegaly and ascites.

   Discussion Top

Hemophagocytic Lymphohistiocytosis (HLH) represents a spectrum of disturbed immunoregulation of variable severity. It encompasses two main conditions like Familial/Primary (FHLH) and Secondary (SHLH), with infection and malignancy.

Familial type is seen in early infancy and childhood, often with history of affected sibling and is invariably fatal. Reported incidence is 1:50000 births.[4] There is fever, hepatosplenomegaly, pancytopenia, reduced cytotoxic T cells, Natural killer cells and accumulation of T lymphocytes and macrophages which engage in hemophagocytosis.[5] Hypercytokinemia involving proinflammatory cytokines mediate the clinical and laboratory features. CNS involvement is frequent with, seizures, irritability, stiff neck, cranial nerve palsy, ataxia and coma.[6]

The secondary type (SHLH) affects patients in any age, may subside spontaneously. Infection associated type is called IAHS and malignancy associated is called MAHS.

The diagnostic criteria proposed by the Histiocyte society is as follows:[4]

A. Clinical criteria

a. Fever

b. Splenomegaly

B. Laboratory criteria

a. Cytopenias affecting at least two of three lineages in peripheral blood

b. Hypertrigliceridemia and or hypofibrinogenemia

C. Histopathologic criteria

a. Hemophagocytosis in bone marrow or spleen or lymph node

b. No evidence of malignancy

The familial type linked to chromosome regions 9q 21.3-22,10q 21-22 performs gene defect, germ line mutations SH2D1A/SAP which is related to X linked Lymphoproliferative syndrome.[7],[8]

Our case satisfies all the criteria required for infection triggered HLH syndrome. However in view of prolonged relapsing course, possibility of a form of FHL cannot be ruled out.

With regard to therapy, Chemotherapy with Epipodophyllotoxin derivatives- Etoposide (VP16), teneposide (VM-26), steroids and intrathecal methotrexate induces remission in familial forms.[10]

Immunoglobulin, antithymocyte globulin and cyclosporin A are also used. Bone marrow transplantation might induce remission.[9],[10] So currently the aim is to achieve clinical remission and prepare for Bone marrow transplant.

An increased incidence of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) in some of these patients is observed, probably related to epipodophyllotoxin. An alternate regime is anti thymocyte globulin, steroids, cyclosporin A, intrathecal methotrexate.[11]

We believe our case is a secondary hemophagocytic lymphohistiocytosis syndrome- infection associated which seems to have a relapsing course with excellent response to immunoglobulin and steroids. Macrophage activation syndrome has to be considered as a differential diagnosis in cases of PUO with hepatosplenomegaly even if there is endocarditis which is not responding to antibiotics.

   Acknowledgment Top

We acknowledge with gratitude all the collaborating departments of Governmentt Medical College, Thiruvananthapuram and special thanks to Prof. Dr. D. Dalus, Medical Superintendent for the financial sanctions for treatment.

   References Top

1.Gerald M fenichel. Clinical pediatric neurology, A signs and symptom approach. 3rd ed. WB Saunders: 2001.  Back to cited text no. 1    
2.Kumar MK, Suresh MK, Dalus D. Macrophage activation syndrome. J Assoc Physicians India 2006;54:238-40.  Back to cited text no. 2  [PUBMED]  
3.Henter JI, Samuelsson-Horne A, Arico M, Egeler RM, Elinder G, Filipovich AH, et al . Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood 2002;100:2367-73.   Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.Henter JI, Elinder G, Öst Å. Diagnostic guidelines for hemophagocytic lymphohistiocytosis. The FHL Study Group of the Histiocyte Society. Semin Oncol 1991;18:29-33.   Back to cited text no. 4    
5.Egeler RM, Shapiro R, Loechelt B, Filipovich A. Characteristic immune abnormalities in hemophagocytic lymphohistiocytosis. J Pediat Hematol Oncol 1996;18:340-5.   Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Henter JI, Nennesmo I. Neuropathological findings and neurological symptoms in 23 children with hemophagocytic lymphohistiocytosis. J Pediatr 1997;130:358-65.   Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Ohadi M, Lalloz MR, Sham P, Zhao J, Dearlove AM, Shiach C, et al . Localization of a gene for familial hemophagocytic lymphohistiocytosis at chromosome 9q21.3-22 by homozygosity mapping. Am J Hum Genet 1999;64:165-71.   Back to cited text no. 7    
8.Clementi R, Zur Stadt U, Savoldi G, Varoitto S, Conter V, De Fusco C, et al . Six novel mutations in the PRF1 gene in children with haemophagocytic lymphohistiocytosis. J Med Genet 2001;38:643-6.   Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Ambruso DR, Hays T, Zwartjes WJ, Tubergen DG, Favara BE. Successful treatment of lymphohistiocytic reticulosis with phagocytosis with epipodophyllotoxin VP 16-213. Cancer 1980;45:2516-20.   Back to cited text no. 9  [PUBMED]  
10.Fischer A, Virelizier JL, Arenzana-Seisdedos F, Perez A, Nezelof G, Griscelli C. Treatment of four patients with erythrophagocytic lymphohistiocytosis by a combination of epipodophyllotoxin, steroids, intrathecal methotrexate and cranial irradiation. Pediatrics 1985;76:263-8.   Back to cited text no. 10    
11.Pui CH, Ribeiro RC, Hancock ML, Rivera GK, Evans WE, Raimondi SC, et al . Acute myeloid leukemia in children treated with epipodophyllotoxin for acute lymphoblastic leukemia. N Engl J Med 1991;325:1682-7.  Back to cited text no. 11  [PUBMED]  


[Figure - 1], [Figure - 2]


[Table - 1]

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