Endgames Picture Quiz

An acquired source of seizures

BMJ 2012; 344 doi: http://dx.doi.org/10.1136/bmj.e2991 (Published 03 May 2012) Cite this as: BMJ 2012;344:e2991
  1. Laura Azzopardi, core medical trainee year 21,
  2. Jennifer Quirk, neurology consultant1
  1. 1South London Healthcare NHS Trust, Department of Medicine, Princess Royal University Hospital, Orpington BR6 8ND, UK
  1. Correspondence to: L Azzopardi laura.azzopardi{at}doctors.org.uk

A 35 year old man came to our hospital by ambulance after a first generalised tonic-clonic seizure witnessed by his wife, with further seizures in the ambulance. Earlier that day he had noticed transient left limb weakness with tremor. He had no symptoms of infection, headache, sore throat, or photophobia. He was independent, otherwise well, had no medical history of note, and was taking no regular drugs, although he had used steroids and protein supplements for body building purposes. He had moved to the United Kingdom from Nepal 12 years earlier but had not recently travelled. There were no other features in the history to suggest risk of immunosuppression.

On assessment, vital signs were within the normal range, with a temperature of 36.2°C. Cardiorespiratory and abdominal investigations were unremarkable. Neurological examination showed an unsteady gait but no neurological deficit. Full blood count, renal function, electrolytes, bone profile, liver function, C reactive protein, and retroviral testing were all normal. Figures 1 and 2 show neuroimaging scans. Lumbar puncture performed after brain scan showed an opening pressure of 20 cm of water, with normal cerebrospinal fluid biochemistry and negative microbiology analysis.

Figure1

Fig 1 Post-gadolinium axial fluid attenuated inversion recovery (FLAIR) magnetic resonance image

Figure2

Fig 2 Post-gadolinium coronal T1 weighted magnetic resonance image

Questions

  • 1 What do the neuroimaging scans show?

  • 2 What is the most likely diagnosis?

  • 3 Which diagnostic procedures support the diagnosis?

  • 4 How would you manage this patient?

Answers

1 What do the neuroimaging scans show?

Short answer

A solitary cystic lesion is seen at the junction of the right frontal and parietal lobes, with an eccentric nodule within.

Long answer

Magnetic resonance imaging shows a well defined lesion at the junction of the right frontal and parietal lobes, with a smooth thin rim of enhancement and a small amount of surrounding oedema (fig 3). The lesion follows the signal intensity of cerebrospinal fluid and is therefore cystic. A small eccentric hyperintense nodule is also seen within the lesion. There are no features of haemorrhage or calcification, and no diffusion restriction was shown on diffusion weighted images. The remainder of the brain appears normal, with no mass effect or midline shift. The location of the lesion in the right precentral gyrus corresponds with the patient’s motor symptoms.

Figure3

Fig 3 Post-gadolinium axial fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging showing a smooth thin rim of enhancement and a small amount of surrounding oedema (arrowheads), with a small eccentric hyperintense nodule within the lesion (arrow)

2 What is the most likely diagnosis?

Short answer

Adult onset seizures in a high risk patient with an intracerebral cystic lesion are suggestive of neurocysticercosis.

Long answer

The differential diagnosis for adult onset seizures includes space occupying lesions, cerebrovascular events, metabolic or toxic insults, infective causes, and focal neuronal abnormalities such as focal cortical dysplasias and mesial temporal sclerosis. Risks identified from the patient’s history are previous use of non-prescription substances and origin from an area endemic for several infectious diseases. The possibility of an infective cause is further supported by the patient’s age. Although the age specific incidence of epilepsy in industrialised countries is bimodal, peaking before the age of 1 year and again after the age of 70, the incidence in developing countries peaks at age 30-40 years owing to acquired neuroinfectious disorders.1

Neuroimaging shows an intraparenchymal cystic lesion with an eccentric hyperdense nodule. This nodule represents a scolex, the knob-like cephalic end of a tapeworm. The most likely diagnosis is therefore neurocysticercosis. In the absence of a scolex, other potential diagnoses to consider with ring enhancing lesions are brain abscess, cerebral amoebiasis, cerebral tumour, toxoplasmosis, and cryptococcal infection.

Cysticercosis is caused by the larval stage of Taenia solium (pork tapeworm), a complex two host parasitic infection.2 Humans are the definitive hosts for adult tapeworms, which result from the ingestion of undercooked pork that contains cysterci. In contrast, swine and humans act as intermediate hosts for the larvae, which are transmitted faeco-orally via ingestion of food contaminated with tapeworm eggs or by autoinfection in humans carrying an adult tapeworm. Once these larvae are ingested, oncospheres hatch and migrate via the intestinal wall to various organs and cause cysticercosis.

Neurocysticercosis refers to cysticercosis of the central nervous system, where cysts undergo four stages of development. The initial vesicular stage may persist for years, with viable cysts and an internal scolex. Vesicular cysts degenerate into colloidal cysts, which leak fluid that generates a strong parenchymal immune reaction. Cysterci then degenerate into nodular lesions and subsequently into calcified granulomas. Cysterci may also be present in the subarachnoid space or ventricles, where they may result in hydrocephalus.

The clinical picture ranges from asymptomatic infection to severe life threatening disease. The most common presentation (70% of cases) is with partial onset seizures (with or without secondary generalisation).3 Other presentations include headache, raised intracranial pressure, stroke, and neuropsychiatric disturbances. Neurocysticercosis is the most common parasitic disease of the nervous system and the most common cause of epilepsy worldwide, accounting for about 10% of newly diagnosed cases.4 It is also increasingly diagnosed in the Western world because of immigration of affected people. Awareness of the condition and its risk factors is essential in making the diagnosis.

3 Which diagnostic procedures support the diagnosis?

Short answer

A diagnosis of neurocysticercosis relies on establishing the risk of exposure and is supported by imaging techniques, immunological tests, and histological examination, although this investigation is rarely needed.

Long answer

Diagnosis of neurocysticercosis relies on clinical suspicion based on exposure history (evidence of household contact, origin from or travel to endemic areas), with support from investigations. Absolute diagnostic criteria are: visualisation of subretinal parasites by fundoscopic examination, cystic lesions showing scolex on imaging, and histological demonstration of parasite from brain or spinal cord biopsy.

Neuroimaging provides information on the distribution and load of neurocysterci, cyst stage, and degree of inflammatory reaction, and it excludes differential diagnoses. Although cystic lesions with a scolex provide a definitive diagnosis, cysts without a scolex that resolve with antiparasitic treatment are also highly suggestive of neurocysticercosis. Computed tomography is best for demonstrating calcified (inactive) lesions, whereas magnetic resonance imaging is better for intraventricular cysts, because it can show oedema and the intracystic changes that indicate stage.

It is crucial to identify the stage of the cysterci because this will influence the treatment strategy. The presence of a vesicular cyst with surrounding oedema indicates relatively recent infection; however, the above case shows that infection may also present several years later. Only in extreme cases where there is diagnostic uncertainty would a brain biopsy be necessary.

Immunological assays, such as enzyme linked immunoelectrotransfer blotting (EITB) of serum and enzyme linked immunosorbent assay (ELISA) of cerebrospinal fluid, are now widely used. Serum EITB is highly sensitive for Taenia solium antigens but less specific for neurocysticercosis than for extraneuronal infection. Meanwhile ELISA using cerebrospinal fluid is 95% specific, although it can be falsely negative when only one lesion is present or the cysterci are non-viable.5

Analysis shows the cerebrospinal fluid to be normal in about half of patients, as it was in our patient. Occasionally it may show mild or moderate pleocytosis with eosinophils or a moderate increase in protein and a raised gammaglobulin concentration.

4 How would you manage this patient?

Short answer

This patient needs antiepileptic drugs and steroids to control symptoms and complications. Antiparasitic agents are not usually indicated in patients with a solitary lesion.

Long answer

Initial treatment of neurocystercicosis focuses on controlling the clinical manifestations that have serious morbidity—seizures, oedema, or intracranial hypertension. Our patient therefore needs to be treated immediately with an antiepileptic agent, which should be continued long term because calcified cysts remain an epileptogenic focus. Rarely, surgical intervention, such as ventricular shunting or excision of a single lesion seizure focus, is indicated for the relief of hydrocephalus that does not respond to medical treatment.

Corticosteroids such as dexamethasone are used to decrease neurological symptoms and cerebral oedema. Higher doses of steroids, and sometimes also immunosuppressants, are recommended before antiparasitic treatment in patients who present with encephalitis or associated vasculitis.

After symptom control, an antiparasitic drug such as albendazole or praziquantel may also be needed depending on the number of neurocysterci present, their location, and their stage of evolution.6 Treatment is therefore tailored to the individual patient, although in general, antiparasitic drugs are needed for symptomatic patients with multiple viable cysterci but not for those with non-viable cysts. Controversy remains on the use of antiparasitic agents for isolated lesions, as in our case.7

Because killing viable cysts provokes an inflammatory response, corticosteroids should be co-administered with antiparasitic drugs. Various studies have indicated that antiparasitic agents reduce seizure activity in patients with epilepsy secondary to active parenchymal cysts.3 8

Finally, patients with epilepsy should receive safety advice, including recommendations on leisure activities and driving, and education on the prevention of tapeworm infection.

Patient outcome

This patient was started on levetiracetam and a tapering dose of oral prednisolone, starting at 40 mg once daily. He sustained two further seizures while on treatment, and a repeat computed tomography scan of the head showed a persisting parenchymal cyst but improvement in cerebral oedema. In view of potentially persistent activity within the cyst, he was given a single dose of albendazole. At further follow-up, he is seizure free and maintains an independent lifestyle.

Notes

Cite this as: BMJ 2012;344:e2991

Footnotes

  • Competing interests: All authors have completed the ICMJE competing interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work, no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

  • Patient consent obtained.

References