2017 NPA-03

This case was originally published in 2017. The information provided in this case was accurate and correct at the time of initial program release. Any changes in terminology since the time of initial publication may not be reflected in this case.

A 36-year-old Hispanic man was discovered unresponsive at home after his family reported hearing him fall. He was an immigrant from Guatemala who reportedly had a history of chronic ethanol abuse and seizures believed to be due to a head injury sustained in a motor vehicle accident several years prior. Emergency medical services responded to the scene and transported him to the hospital. Resuscitative efforts failed, and death was pronounced in the emergency department. An autopsy was performed.

Brain and dura mater

The whole slide image provided is an H&E stain from a brain autopsy.

At autopsy, the patient was a well-developed, well-nourished man with no lethal injuries or visceral disease. Postmortem toxicology testing was negative for illicit drugs and ethanol. Neuropathologic examination revealed multiple tan-white dural-based (Image A and Image B) and intraparenchymal (Image C) encapsulated masses, each measuring approximately 1 cm in greatest dimension. No traumatic brain injuries were identified. Microscopic evaluation demonstrated encysted, degenerated helminths with undulating gut lumina (Image D), cholesterol clefts (Image E), and partial scolices (Image F). Cyst walls were fibrotic with chronic inflammatory infiltrates and multinucleated giant cells. The surrounding brain parenchyma was markedly gliotic with scattered Rosenthal fibers and scant hemosiderin deposition. Cause of death was determined to be seizure secondary to neurocysticercosis (Taenia solium infection).

Parasitic infections of the CNS are often endemic to certain geographic regions and may present as seizure disorder. Neurocysticercosis is the most common parasitic infection of the CNS and is the leading cause of acquired epilepsy worldwide. It is caused by the pork tapeworm Taenia solium, a cestode helminth endemic to Latin America, Africa, Southeast Asia, and the Western Pacific Region. Human CNS infection occurs by ingestion of eggs in fecally-contaminated food or beverage. Eggs develop into larval forms in the small intestine and subsequently migrate to distant sites. Encysted larval forms (cysticerci) may develop in the CNS, skeletal muscles, soft tissues, liver, and lungs. Larval forms in the brain grow slowly over years, becoming encysted before dying. Degenerated cysts are often fibrotic and calcified and typically occur in association with the leptomeninges or ventricles. Viable larvae in the brain appear on CT as hypodense, circumscribed cysts ranging from approximately 0.5 to 2 cm in diameter. Death of cysticerci in the CNS and subsequent leakage of cyst contents elicits a local inflammatory reaction which can result in seizure, headache, increased intracranial pressure, psychiatric symptoms, and focal neurologic deficits.

Paragonimus westermani, also known as the oriental lung fluke, is a trematode helminth. Paragonimiasis - due most commonly to Paragonimus westermani infection - is endemic to Asia and West Africa. CNS involvement, which usually results in focal neurologic deficits or seizures, occurs in a minority of infected patients. Serum and cerebrospinal fluid eosinophilia is common. Neuroimaging often demonstrates ring-enhancing mass lesions with surrounding edema and mild mass effect. Human infection occurs by ingestion of contaminated crabs or crawfish containing encysted larval forms (metacercariae) which hatch in the gastrointestinal tract of the human host and migrate from the small intestine to the lung and, less commonly, the brain. The larvae then become encapsulated and mature into adult trematode organisms over two to three months. Lung lesions, which produce symptomatic hemoptysis, tend to be nodular or cavitary on radiographic examination. Eggs laid in the lungs exit the human host through sputum or are swallowed and excreted to continue the life cycle. Eggs laid in the brain are retained and, along with the adult worm, elicit abscess or granuloma formation. Longstanding cases of paragonimiasis may exhibit characteristic “soap bubble calcifications” in the brain.

In addition to helminths, protozoal brain infection can also result in seizures. The protozoan Plasmodium falciparum can cause cerebral malaria, a common infectious etiology of seizures. CNS involvement affects approximately 1% of infected individuals and carries a mortality rate of 15% to 20%. Endemic to tropical and subtropical regions, P. falciparum is transmitted via the bite of the Anopheles mosquito through which sporozoites enter the human host blood stream and travel first to the liver, where they invade hepatocytes and develop into schizonts. Rupture of schizonts releases numerous merozoites back into the blood stream where they invade red blood cells to re-initiate the erythrocytic cycle. Infected red blood cells adhere to small venules in the brain via PfEMP1 (P. falciparum erythrocyte membrane protein-1) surface membrane proteins produced and can result in vasospasm, increased intracranial pressure, obstructive hydrocephalus, acute cerebral infarction, and diffuse encephalopathy. Survivors of acute infection may demonstrate multifocal cortical disruptions in affected regions, which can become epileptogenic foci.

Differential diagnosis of seizures due to CNS infections in the United States requires a high index of suspicion when the patient is an immigrant, as parasitic infections of the CNS are endemic to various regions outside of the United States. Immigration status, as well as social and travel history, are essential elements of clinical history when evaluating seizure patients.

• Neurocysticercosis, helminth infection by Taenia solium, is the most common parasitic infection of the CNS and is a leading cause of epilepsy worldwide.
• Neurocysticercosis is endemic to Latin America, Africa, Southeast Asia and the Western Pacific Region.
• Paragonimiasis, helminth infection by Paragonimus westermani, is less common worldwide than neurocysticercosis, but the majority of patients with CNS involvement develop seizures or other neurologic deficits.
• Cerebral malaria, caused by the protozoan Plasmodium falciparum, is endemic to tropical and subtropical regions of the world.

This case was originally published in 2017.

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