Recurrent cerebral larva migrans: A case report and review of literature.

Cerebral larva migrans (CLM) is an uncommon and rarely diagnosed entity. We report here a histopathologically proven case of CLM in a 13 year-old girl, who presented with bilateral focal seizures, right hemiparesis, and lapsed into altered sensorium prior to admission. Her CT scan was suggestive of a granulomatous lesion which eventually turned out to be CLM (toxocariasis). Interestingly, the lesion recurred after excision, with a confusing clinical picture. Following the second surgery, the pathology was reconfirmed and cure was provided for the disease. There has been no further intracranial recurrence during the past ten years although she developed cutaneous lesions.

Introduction

Toxocariasis is a widespread native parasitosis[1-6] caused by -type nematode larvae that is manifested as various clinical symptoms. It is usually transmitted by dogs and rarely, by cats. Contamination may occur by ingestion of embryos deposited on the ground. It is commonly seen in children younger than 12 years of age in rural areas.

The clinical syndromes are nonspecific, but frequent. They constitute neurological, ophthalmological, pulmonary, cutaneous, and sometimes, rheumatological varieties. Cerebral toxocariasis is a rare disease and is difficult to diagnose preoperatively. Although visceral larva migrans caused by is relatively more common, there has been some very rare histological documentation of cerebral involvement.

Case Report

A 13 year-old girl presented to our neurological services with a history of recurring episodes of left focal motor seizures of 16 weeks’ duration and right focal motor seizures of eight weeks’ duration. She also developed vomiting and diffuse headache which progressively worsened over six weeks. She had progressive left hemiparesis and lapsed into altered sensorium a day prior to admission.

On examination, vital parameters were found to be normal and general physical examination did not reveal any specific abnormality. She was in altered sensorium, opening her eyes to pain and able to localize the pain with her right upper limb. She had areflexic, flaccid left hemiplegia; there were no meningeal signs. A clinical diagnosis of right supratentorial mass lesion was made.

Laboratory investigations revealed marginally elevated WBC count (8900 cells/cu. mm) and elevated ESR (40 mm 1st hour). Her eosinophil count was normal (2%) as were her chest X-ray and ultrasound of the abdomen and pelvis. CT scan of the brain (plain and contrast) revealed a right frontoparietal parasagittal mass lesion with a contrast-enhancing ring, perilesional edema, and a central cystic component. There was another smaller and similar lesion in the opposite frontal lobe [Figure 1].

Figure 1

Preoperative CT scan before 1st surgery

She underwent right frontoparietal parasagittal craniotomy. A yellowish, firm, avascular lesion with areas of necrosis was found intraoperatively. There was a good plane of cleavage with no dural involvement or attachment. Near total excision of the lesion was done. A tiny nodule firmly attached to a large cortical draining vein was left behind.

Histopathological evaluation of the mass revealed nodular congregations of histiocytes and lymphocytes with occasional giant cells. There was marked fibrosis extending into the parenchyma, dividing it into nodular areas. Focal rounded calcified areas were seen with a concentric lamellar structure along the exterior. There were areas of gliosed brain parenchyma and reactive astrocytosis with chronic inflammatory response. These features are typically suggestive of toxocariasis [Figure 2].

Figure 2

Histopathology–Right frontal lesion

Her sensorium improved completely postoperatively and her left hemiplegia improved to grade 4/5 with physiotherapy. She was given a full course of Albendazole and was on anticonvulsants during follow-up.

After one month, her seizure frequency had increased and her headache and left hemiparesis worsened. A repeat CT scan revealed the recurrence of the lesion in the right posterior frontal parasagittal region. The mass lesion had a contrast-enhancing ring with perilesional edema. The lesion on the opposite side was similar in size compared to the previous scan [Figure 3]. She was re-operated upon when the lesion was found to have regrown and was similar to that at the time of the prior surgery. The lesion was completely excised this time, while preserving the cortical veins. She made a rapid postoperative recovery and her seizures were well controlled with anticonvulsants. Follow-up MRI revealed that the lesions had not increased further [Figure 4].

Figure 3

Preoperative CT before 2nd surgery

Figure 4

Postoperative MRI T1 Wt after 2nd surgery

Six months later, she again presented to us with two episodes of generalized seizures and right hemiparesis. MRI of the brain revealed an increase in the size of the left frontal lesion with no evidence of any lesion on the right side [Figure 5]. She was given a trial of steroids with which she marginally improved. A repeat CT scan of the brain done two months later revealed further enlargement of the ring-enhancing lesions in the left frontal parasaggital region [Figure 6]. She underwent left frontoparietal craniotomy and total excision of the granuloma. Detailed histological examination revealed foci of necrotic debris surrounded by a florid inflammatory response containing numerous plasma cells, lymphocytes, and neutrophils. Occasional Langhans or foreign body giant cells were also noted; there were no epitheloid granulomas. Small foci of oval to round calcifications were also seen. The adjoining parenchyma showed intense perivascular cuffing by chronic inflammatory cells and a diffuse microglial proliferation. Reactive astrocytes were present at the periphery. Special stains for fungi and acid fast bacilli were negative [Figure 7].

Figure 5

Preoperative MRI T2 Wt before 3rd surgery

Figure 6

Preoperative CT scan (after steroid therapy) before 3rd surgery

Figure 7

Histopathology of left frontal lesion

About eight years after the first diagnosis, she developed unusual skin lesions over the shin of both the legs [Figure 8]. Biopsy of the lesion done at a different center was reported to show a lymphocytic inflammatory response. She partially responded to a course of albendazole and dermatological applications. Repeat MRI scans after eight and ten years reveal no recurrence [Figures 9 and 10].

Figure 8

Skin Lesions

Figure 9

Follow-up MRI after eight years

Figure 10

Follow-up MRI after ten years

Discussion

Several roundworm parasites of domestic animals can infest humans. [1-8] It is usually the larval stages of these parasites (‘larva migrans’) which provoke clinical symptoms in humans. The Toxocara species, the ascarids found in dogs and cats, are most commonly associated with larva migrans. infections are extremely common (up to 90–100%) in puppies less than three months of age, and can also occur in older dogs. In the United States, the seroprevalence of infection in children varies from 2–10%. Internationally, it is almost the same or slightly higher. Infection rates are higher among African Americans and Hispanic Americans, probably because of greater exposure to the parasite.[7-9]

This infection is mostly seen in children under twelve years of age, more so in rural areas than in urban areas. It is worldwide in distribution and Pica (geophagia) is a known risk factor. Raw liver (beef, chicken, sheep) are sources of infective larvae. , the common roundworm in the dog, can cause visceral larva migrans (VLM) syndrome in humans, which may include generalized illness, eosinophilia, and symptoms arising from larval invasion of different organs. Of these, the clinically significant organs are the liver, lungs, eyes, and the CNS. [2-71011] , a roundworm infection of raccoons, is emerging as an important helmenthic zoonoses.[1213] There are also reports of VLM associated with .[14] Children can present with fever, marked hepato-splenomegaly, wheezing, and rales. It can also manifest in a severe form—seizures, myocarditis, encephalitis, pruritic rash, or urticaria. Periorbital edema and strabismus also have been reported in some children with VLM. Usually, a differential diagnosis of allergies, eosinophilia-myalgia syndrome, neoplasia, or other parasitic infection is made.

Humans, especially children, contract Toxocara infections by ingesting embryonated eggs. The larvae hatch in the small intestine, invade the mucosa, and enter the portal system. The larvae proceed to the lungs and the circulatory system where they can disseminate virtually to every organ. Clinical manifestations depend upon the extent of tissue damage caused by the invading larvae and the associated immune-mediated inflammatory response.

Cerebral toxocariasis is a rare disease and difficult to diagnose clinically. It can present as encephalitis or mass lesions. [12-21] Patient characteristics and history, clinical symptoms and signs, positive serology, eosinophilia, and increased levels of IgE are helpful markers in defining toxocariasis. Computed tomography (CT) and magnetic resonance imaging (MRI) may reveal multiple cerebral lesions in patients with central nervous system involvement. Pathological CT or MRI with solitary mass lesions has been only described in seven cases.[22-25] Histopathology findings are crucial adjuncts to the final diagnosis.[26]

Eosinophilia may be present, but it is nonspecific as it is found in many parasitosis;[1117] children may be anemic. Stool cultures may be done to rule out other parasitic infections. Elevated titers of isohemagglutinins to the A and B blood group antigens support the diagnosis of VLM. Enzyme-linked immunosorbent assay (ELISA) with excretory-secretory antigen (TES-Ag) has a reported sensitivity of 78.3% and specificity of 92.3%. The increase of antiTES Ag IgE level means the acute or progress of inflammation due to toxocariasis. Tests can be confirmed by Western Blotting which may be more specific than ELISA. Hypergammaglobulinemia may be present in some patients.[27-29]

Our case had several rare and interesting features. The clinical presentation was like a typical mass lesion; CT and MRI were also suggestive of mass granulomatous lesion. The most unusual feature in our case is the recurrence from a small residual lesion, probably triggered by exaggerated host immune-mediated response. Although recurrence has challenged the diagnosis, detailed histology has reconfirmed larva migrans. Probably a small residue contained part of the larva migrans which happened to trigger the inflammatory response. Surprisingly, albendazole and steroids did not help regression or arrest of the process. Rapid resolution of the symptoms and recovery of deficits following the second surgery proves the role of radical removal of these lesions. In a tropical country like India, granulomatous lesions such as cysticercosis, tuberculosis, and fungal granulomas need to be considered as differential diagnoses. Developing cutaneous ulcerative lesions after several years is another interesting feature. The overall combination of cerebral and cutaneous manifestations at different times has not been described in literature.

Therapy is aimed at relieving symptoms and is intended to diminish the host inflammatory response to the parasite. Corticosteroids and antihistamines are often used for this purpose. Patients with myocarditis or central nervous system disease should always be treated with corticosteroids. Among the available drugs, albendazole is the most commonly used. The recommended dose of albendazole is 15 mg/kg body weight daily for five days, and in some cases with VLM syndrome, the treatment needs to be repeated.[30-32] An evaluation of treatment efficacy can be made by observing a rise in eosinophilia within a week, followed by any improvement in clinical symptoms and signs, lower eosinophilia, and serological tests taken over a period of at least four weeks. Attempts should be made to identify the source of infection and treat infected puppies and kittens with appropriate anthelminthic agents.

A rare case of cerebral larva migrans with unusual clinical features and radiological appearance is presented herein. Recurrence due to a small residue after earlier surgery is unusual. Subsequent total excision has resulted in complete recovery and a good outcome.