Acute disseminated encephalomyelitis: Extremely rare presentation of pediatric human immunodeficiency virus infection.

Acquired human immunodeficiency virus (HIV) infection in a 10-year-old child, presenting with monoparesis, progressing to triplegia over 4 weeks is an extremely rare feature. The child had left upper motor neurone facial palsy with left hemiplegia, paralyzed right lower limb, grade zero power, exaggerated deep tendon reflexes and bilateral extensor plantars. Child tested positive for HIV by ELISA. CD3(+) absolute count was 431. CD3(+) CD4 count was 28, and CD45 absolute count was 478. Magnetic resonance imaging of brain and spine showed multiple ill-defined foci of hyperintensity in white matter suggestive of ADEM. Acute demyelinating encephalomyelitis (ADEM) is an extremely rare presenting feature of perinatally acquired HIV infection in paediatrics. Clinically child remained same even with methylprednisolone, intravenous immunoglobulin, antituberculosis therapy, trimethoprim-sulfamethoxazole prophylaxis and supportive therapy. Child had sudden clinical deterioration and death before antiretroviral therapy could be initiated. This case emphasizes that pediatricians and neurophysicians should suspect HIV as an etiology of ADEM in cases with atypical clinical presentation and social risk factors, in spite of its very rare occurrence.

Introduction

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated, acute severe, demyelinating disorder involving central nervous system (CNS) white matter, characterized by diffuse neurologic signs and symptoms coupled with evidence of multifocal lesions of demyelination on neuroimaging.[123] ADEM is commonly seen following exanthematous viral infections (measles, small pox, chickenpox, Epstein-Barr virus, influenza, mumps, rubella, hepatitis, herpes simplex, coxsackie, Mycoplasma, Campylobacter, Streptococcus, Legionella, Rickettsia), systemic infections, or vaccinations.[12] Human immunodeficiency virus (HIV)-infection presenting as ADEM is extremely rare in pediatric literature.[456] Two pediatric and four adult cases reports of ADEM in HIV-infection have been reported.[17891011]

Case Report

A 10-year-old male child, first in order of birth, presented with weakness in both lower limbs and left upper limb since 1-month. Weakness was first noticed in left lower limb which progressed to right lower limb and left upper limb leading to complete loss of limb movements. The right upper limb was normal. Child did not have fever, exanthematous illness in recent past, seizures, vision disturbances, altered sensorium, vomiting or headache. Child was born by home delivery, had average birth weight with uneventful postnatal period and was never immunized. Child was breastfed for 2 years. Of the two younger siblings, an 8-year-old male child is well and asymptomatic, but a younger female child had expired due to pneumonia at the age of 2 years. Child had normal developmental milestones, and his weight was 27.5 kg (25th centile), height was 138 cm (50th centile), head circumference was 50.5 cm (50th centile), underweight for his age. Two years back child was diagnosed and treated completely for tuberculous lymphadenitis.

Course of illness

Child was admitted to our hospital on 28th day of illness with evaluation and investigations done at another hospital where he was admitted for 2 weeks. Investigations done there were Hb-10.8 gm/dl, leucocytes 4800 (polymorphs 56%, lymphocytes 44%, platelets 3.5 lakhs/mm3, malarial antigen was negative and Regulatory focus theory was normal. Cerebrospinal fluid (CSF) study had 61 cells, all lymphocytes, proteins (43.61 mg/dl) sugar (36 mg/dl), and no growth on culture. Ultrasound abdomen showed multiple discrete nonnecrotic mesenteric lymphadenopathy. Magnetic resonance imaging (MRI) spine (probably suspecting lower motor neuron lesion) and screening of brain revealed features of ADEM not correlating with clinical history [Figures 1 and 2]. Child received methyl prednisolone, and had no clinical improvement. Child developed high grade fever and diarrhea following which parents got him discharged against medical advice. On admission to our hospital, patient was averagely built and nourished, pale, conscious, oriented and had multiple healed pyoderma lesions. Neurological examination revealed left sided upper motor neuron (UMN) facial palsy, grade I power in right lower limb and grade II power in left upper and left lower limb, bilateral extensor plantars s/o left hemiparesis with UMN facial palsy which progressed to triplegia in next 36 h. Signs of meningeal irritation were absent, and fundus examination was normal. Child had firm hepatomegaly measuring 3 cm, without splenomegaly.

Figure 1

Flair axial image reveals large hyperintensity in genu and posterior limb of internal capsule, ventral thalamus and part of lentiform nucules

Figure 2

Flair coronal image reveals large area of hyperintense signal in right gangliocapsular region (right > left)

In view of clinical presentation not correlating with examination, investigations and MRI findings, possibility of immunocompromised state was suspected. Child was detected positive for HIV 1 by ELISA. Mother also tested positive for HIV. Present clinical status of AIDS in a child, demanded early initiation of highly active antiretroviral therapy (HAART). Due to unavailability of ART center at our hospital patient was referred to another institute. Parents gave negative consent for lumbar puncture and CSF investigations. Serological IgM titers for TORCH, Mantoux test, HbsAg, and hepatitis C virus were negative. CD3+ absolute count was 431 (range of 690-2540). CD3+ CD4 count was 28 (range of 410-1590), and CD45 absolute count was 478. High resolution computed tomography detected features of Pneumocystis jiroveci pneumonia. Patient was treated with intravenous immunoglobulin (IVIG), methylprednisolone, antituberculous therapy, trimethoprim-sulfamethoxazole in therapeutic and prophylactic doses along with other supportive care. Child had sudden deterioration followed by death before initiation of HAART.

Discussion

Acute disseminated encephalomyelitis is an extremely rare presenting feature of HIV-infection in children.[4567] There are two pediatric and four adult cases reported of ADEM in HIV-infection.[17891011]

Tullu et al. reported an 8-year-old male child with paraparesis, focal seizures and MRI Brain suggestive of ADEM, hence treated with methyl prednisolone Patient had transient improvement, followed by clinical deterioration. Due to an unexpected response to therapy and presence of social risk factor, patient was tested for HIV. Patient was detected positive for HIV and had rapid deterioration, followed by death due to concomitant Herpes zoster on day 10 of ART along with antiviral and antituberculosis drugs. This was the first case reported of perinatally transmitted HIV-infection presenting as ADEM.[7]

van Toorn et al. have described a 7-years-old HIV-infected child who developed cryptococcal meningitis, with raised intracranial pressure, complicated by ADEM and disseminated herpes simplex infection 3 weeks after commencement of HAART.[8]

Narciso et al. had described a 27-year-old female with fever, clouding of consciousness, paraplegia, sensory loss, and blindness (due to ADEM), as manifestations of primary HIV-infection.[9] Mogensen et al. have reported a 45-year-old bisexual male with clinical symptoms (cognitive dysfunction and right hemiparesis), MRI, and CSF examination findings suggestive of acute demyelinating encephalomyelitis as the initial presentation of primary HIV-infection.[10] Allen et al. had reported a 32-year-old homosexual male presenting with behavioral changes and diagnosed as acute demyelinating encephalomyelitis with a 5 year-old history of HIV-infection.[11] Raychaudhuri et al. have described a 31-year-old woman diagnosed as hemorrhagic ADEM in an HIV-infected patient presenting solely with acute onset bilateral blindness (with normal retina) and hemiparesis.[1]

The prominent differences noted in our case were, delayed age of presentation, preserved nutritional status, absence of recent viral infection, clinical history, and examination had significant disparity. Clinically, child remained the same without improvement following IVIG and methyl prednisolone therapy and had rapid deterioration and death before initiation of HAART.[78]

Clinical manifestations of ADEM include alteration of sensorium, motor/sensory deficits, cranial neuropathies, seizures, and ophthalmoplegia.[23] Our patient had predominant motor and cranial nerve involvement not correlating with the previous pediatric and adult case reports.[17891011] This can be a part of the clinical spectrum of HIV-induced ADEM and needs further evaluation and study of more cases. The opportunistic CNS infections such as tuberculosis, toxoplasma, cytomegalovirus, Cryptococcus, herpes simplex virus, John Cunningham virus produce multifocal intracranial lesions in children.[121314]

Acute disseminated encephalomyelitis is being recognized more frequently with increasing use of MRI as happened in our patient; neurodiagnosis of ADEM was done at previous institute, without etiological diagnosis. MRI spine and brain of our patient showed evidence of multiple ill-defined foci of T2-weighted image and fluid attenuated inversion recovery hyperintensity involving right thalamocapsular region, right posterior limb of the internal capsule, right globus pallidus, bilateral hippocampus and subcortical white mater of right parietal lobe suggestive of ADEM. Areas of altered SI showing heterogeneous contrast enhancement involving the dorsal cord with areas of cord expansion were also seen [Figures 1 and 2]. The MRI findings of our patient were consistent with observations mentioned by Murthy et al.[278]

We suspected and diagnosed HIV as a cause of ADEM in our patient based on history not correlating with clinical examination, presence of sociocultural risk factors like home delivery, prolonged breast feeding, poor health care awareness, younger siblings death due to pneumonia, which reflected significant ignorance in availing health care facilities for delivery and immunization for the child.[7] Furthermore, patient's nutritional status, pallor, chronic healed pyoderma lesions with hyperpigmentation, nonspecific abdominal distension, mild tachypnea, past tuberculous lymphadenitis were significant contributory factors to suspect multisystem chronic infection with immunosuppression.[4]

Though extremely rare, perinatally acquired HIV-infection must be suspected in a child with social risk factors, atypical clinical presentation with neurological examination and neuro-radiodiagnosis findings of ADEM.[7]