A tropical menace of co-infection of Japanese encephalitis and neurocysticercosis in two children.

Japanese encephalitis (JE) is a mosquito borne encephalitis caused by Flavivirus. Neurocysticercosis (NCC) is a parasitic disease of the central nervous system caused by Taenia solium. In this report, we describe the clinical profile, imaging findings, and outcome of two children with JE and coexisting NCC. Eleven and thirteen-year-old boys from the same town of Jharkhand state were brought with history of fever, seizures, altered sensorium, and extrapyramidal symptoms. Dystonia, hypomimia, bradykinesia, and dyskinesia were observed. Meige syndrome observed in one of the children is a novel finding. Magnetic resonance imaging of the brain revealed findings suggestive of JE with cysticercal granulomas. There are few reports of coexistence of JE and NCC in children. Both children were treated with ribavirin, and follow-up imaging had shown significant resolution of signal changes. Both the children had shown marked clinical improvement. Ribavirin was found to beneficial in reducing the morbidity in our patients.

Introduction

Japanese encephalitis (JE) is a mosquito borne encephalitis caused by Flavivirus with a case fatality of 25% and nearly 50% with JE infection recover with sequelae.[1] Neurocysticercosis (NCC) is caused by Taenia solium, an intestinal tapeworm. There are few reports of coexistence of JE and NCC in children. In this report, we describe the clinical profile, imaging findings, and outcome of two children presenting with JE and coexistent NCC.

Case Reports

Case report 1

An 11-year-old boy from Jharkhand was brought with history of fever, headache, seizures, altered sensorium and left sided weakness since 1 month. At the onset, he had high-grade fever for 5 days and headache, photophobia, and vomiting for 2 days. He had three brief episodes of generalized tonic-clonic seizures, and there was a progressive drop in sensorium requiring hospitalization for 20 days. He also had weakness of the left upper and lower limb and repetitive perioral twitching movements. He was managed elsewhere, and was brought to our institution due to inadequate clinical improvement. There was an outbreak of encephalitis in their geographical area.

The child was in a minimally conscious state, and nutrition was maintained through nasogastric feeds. Fundus was normal. Asymmetric spasticity involving left more than right with brisk deep tendon reflexes were observed. Bilateral plantar responses were extensor. Perioral dyskinesia and striatal toe were observed.

Magnetic resonance imaging (MRI) brain [Figure 1a and b] revealed hyperintensity involving bilateral basal ganglia, thalami, substantia nigra, and hippocampi. There was a cysticercal granuloma in the right posterior temporal lobe [Figure 1c] with ring enhancement and perilesional edema [Figure 1d].

Figure 1

T2 fluid attenuated inversion recovery and T2 axial images (a and b) show symmetric hyperintensity of caudate, thalami (white arrows) and substantia nigra (white arrow). Neurocysticercosis lesion is seen in the right posterior temporal region (white arrows in c and d). Repeat imaging after 4 months showing complete resolution of signal changes (white arrows in e and f). Cysticercal granuloma is largely unchanged in size and enhancement (white arrows in g and h)

Case report 2

A 13-year-old boy from the same town was brought with a history of fever, headache, and altered sensorium from the 1st day of illness and abnormal involuntary movements of limbs and oromandibular muscles since 3 months. The initial cerebrospinal fluid (CSF) analysis was normal. His sensorium improved after 4 days of treatment elsewhere. At the end of 1st week of illness, he had abnormal intermittent twisting movements of left followed by right-sided involvement which disappeared during sleep. He had forcible involuntary closure of both the eyes and had difficulty in opening his eyes spontaneously. He had hypophonia, difficulty in chewing and swallowing solid foods. Child was brought to our institution for management of intermittent fever and extrapyramidal symptoms.

The child was conscious and oriented. Disarticulation due to oromandibular dystonia was observed. Blepharospasm, hypomimia, and bradykinesia were observed. Fundus examination was normal, and there was generalized dystonia with perioral dyskinesia. Rigidity involving all four limbs was observed but his ambulation was preserved. Muscle stretch reflexes were normal. Plantar responses were flexor.

MRI brain [Figure 2a–c] revealed asymmetric areas of hyperintensity involving the frontal, temporal, parietal lobes, caudate, and thalami. T2 weighted images had shown cysticercal granulomas in the right cingulate gyrus [Figure 2d] and right inferior frontal gyrus [Figure 2f]. Ring enhancement were seen in postcontrast images [Figure 2e and g].

Figure 2

T2 fluid attenuated inversion recovery imaging (a-c) shows gyral swelling and hyperintensity with asymmetric bifrontal and bitemporal involvement (white arrows). Substantia nigra hyperintensity is also seen bilaterally (black arrow). Bilateral thalamic and caudate nuclei involvement are seen on image b (yellow arrows). (d) Colloid vesicular stage cysticercal granuloma is seen in the right cingulate gyrus with ring enhancement on postcontrast study (e). Another granuloma is seen in right inferior frontal lobe (white arrow in f) with ring enhancement (white arrow in g)

Laboratory findings of both children are summarized in Table 1. Based on the history, clinicoradiological and serological evidence, diagnosis of co-infection of NCC with JE was established. First case was managed with supportive measures, anticonvulsants, and anti-spasticity medications. Second case was managed with clonazepam, tetrabenazine, and trihexyphenidyl. Both these children were managed with oral ribavirin 10 mg/kg/d in divided doses for seven days as there was a persistence of cytotoxic oedema. Neurorehabilitation measures were initiated. There was a minimal improvement of sensorium and extrapyramidal symptoms at discharge in Case 1, and a minimal reduction of perioral dyskinesia was observed in the second case.

Table 1

Summary of laboratory investigations

Follow-up assessment after three months had shown significant reduction of oromandibular dystonia and hand dystonia and there was no blepharospasm in Case 2. Repeat MRI [Figure 3a and b, d–g] had shown significant resolution of gyral swelling with residual hyperintensity in the right frontal lobe, complete resolution of signal changes in thalami and basal ganglia, lateral ventricular prominence, and unchanged granulomas with persistent ring enhancement. However, computed tomography (CT) brain confirmed eccentric calcified scolex in both lesions [Figure 3c]. Follow-up assessment after 4 months in Case 1 had shown a residual left hemiparesis and dystonia with normal ambulation. Repeat imaging [Figure 1e–h] showed complete resolution of signal changes while the granuloma remained unchanged in size and enhancement with interval reduction in perilesional edema. CT brain revealed no calcification and he was treated with prednisolone 1 mg/kg/d for 5 days and albendazole 15 mg/kg/d for 28 days.

Figure 3

Repeat imaging in Case 2 shows complete resolution of signal changes in thalami, basal ganglia (white arrows in a), mild right frontal hyperintensity (white arrow in b). T2 axial and fluid attenuated inversion recovery images (d and f) show the residual cysticercal granulomas and T1 postcontrast images (e and g) show persistent enhancement. Computed tomography brain done at the same time (c) shows calcified granuloma

Discussion

Population from geographic areas with rice farming fields are at risk of contracting JE by Culex tritaeniorhynchus and Culex vishnui mosquitoes.[2] Avian or swine species acts as the amplification host, and humans and equines are incidental hosts. Diagnosis of JE is established by testing of paired CSF and blood for specific neutralizing antibodies against JE viral antigen and/or detection of viral antigen in CSF. NCC is transmitted by faeco-oral route and disease is widely prevalent in India, China, Africa, Latin America.[3] NCC usually presents with seizures, raised intracranial pressure, hydrocephalus, or cysticercal encephalitis and diagnosis is established by neuroimaging.

Coexistence of NCC and JE had been described as early in 1940 by Hsu.[4] A large series found a high prevalence of 37.5% patients with a coexistent NCC and JE based on serology, imaging or autopsy findings. In this series, only 11% cases had definite NCC lesion on imaging or autopsy while remaining were diagnosed based on the anti-cysticercal antibodies in CSF and high prevalence could possibly be due to false positivity encountered with serology testing for NCC or antibodies produced as a result of intestinal infection.[5] It has been postulated that co-infection of JE and NCC might be synergistic and not simply a coincidence.[6] In patients with NCC, there might be an altered immune response and facilitated invasiveness of JE virus.[7]

Clinical presentation of children with coexistence of JE and NCC is similar to patients with JE alone. Meige syndrome observed in Case 2 is a novel feature in JE and could be explained by the lesions in basal ganglia. Previous reports of children with JE observed fever and seizures in almost all patients, headache in 70-80% and vomiting, focal deficits, extrapyramidal symptoms or meningeal signs in 30-50%.[89] Kalita et al. found that dystonia was significantly more in children while radiological findings were similar in children and adults with JE.[10] Detection of JE virus RNA by polymerase chain reaction in CSF was negative in our patients as it was not tested in the early phase of illness and the toxaemia period is short.

Observation of asymmetric gyral lesions in the side harboring NCC in Case 2 was in concordance with previous reports.[7] In our patients, the late persistence of active changes could possibly be due to coexistent NCC. Signal changes involving basal ganglia, thalami, brainstem, hippocampi and cerebral cortex had been reported in patients with JE. These findings were more pronounced in the side harboring the NCC or with greater number of cysts.[6] Similar observation was found in one of our patients. On contrary, Azad et al. have found that 3% patients had coexistent other intracranial pathology, and the site of NCC lesion did not predict the severity of coexisting disease.[11]

Our patients were treated with ribavirin and had shown significant improvement during follow-up. A previous randomized trial of ribavirin found no reduction of early mortality or morbidity in patients with JE.[12] Enhanced personal hygienic measures, environmental sanitation, vector control, mass vaccination strategies are needed to prevent disease outbreak.

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Conflicts of interest

There are no conflicts of interest.