Pathology of Neurocysticercosis in Children

Pathophysiology

• NCC classification: NCC is classified by its location.  There are parenchymal, extraparenchymal (subarachnoid-cisternal and intraventricular termed racemose cysticercosis), and spinal forms.
• Intraparenchymal NCC: Intraparenchymal cysts may be single or multiple. Single cysts are also referred as single enhancing lesions or single cyst granuloma.
• Cysticercosis stages: Cysticercus passes through a sequence of four morphological stages with each having a different appearance on neuroimaging : the vesicular stage, where it contains a living larva; the colloidal stage as the larva degenerates but still has liquid contents; the “granulonodular” stage, as the membrane of the cyst thickens; and the final stage of calcification (1,2,9,28).

Life cycle

The life cycle of T. solium involves humans and pigs. Humans are the definitive hosts, acquiring intestinal infection (taeniasis) from pigs, the intermediate hosts, by ingestion of undercooked pork infected with live cysticerci (encysted larvae). Humans also acquire cysticercosis via consumption of food or water contaminated with T. solium eggs or by autoinfection (1).

• Adult form T. solium: The adult worm is found in the small intestine of humans. Cysticerci are the larvae of T. solium, usually hosted in swines (10).
• Anatomy of T. solium: The tapeworm of T. solium is white in color and measures 2 to 3 meters in length. Its head, the scolex (an intracystic nodule in the larva) is round or slightly elongated, containing suckers and protruding hooks, or rostellum, through which it attaches to the host intestinal wall. The body consists of several segments known as proglottids, and each one acts as an independent reproductive unit containing both male and female reproductive organs. (1,5,8).
• Development of tapeworm: The adult tapeworm develops when humans ingest raw or undercooked pork containing cysticerci. The larvae are released in the small intestines where they develop into the adult worm, attaches to the intestinal wall, and liberates eggs.
• The pig is the intermediate host: T. solium eggs shed in human feces are consumed by free-roaming pigs that ingest them directly or indirectly through contaminated agricultural products or water. Once consumed, the larvae are released from the eggs and encyst in porcine muscle (cysticerci), completing the cycle (1,5,8).
• T. solium can cause two diseases in humans: Taeniasis, the intestinal infection with the adult tapeworm, and cysticercosis, caused by cystic larvae or cysticerci (8,32).
• Human cysticerosis infestation: Humans are infested by T. solium eggs present in contaminated water, vegetables, or fruit (heteroinfestation) either because of poor hygiene habits or by soil fertilized with human feces. Self-infestation occurs when individuals are contaminated by their own feces, ingesting eggs or proglottids of their own tapeworm (1,5,8).
• The hexacanth: The embryonic form of the cysticercus, which reaches the CNS through the bloodstream, lodges in the brain parenchyma by occluding capillary vessels usually at the gray-white junction. Embryos actively cross the capillary wall and reach the interstitial space where they evolve to the cystic form, transforming into cysticerci (1,5,8,17).

Live larvae are only seen in cysts in the vesicular and colloidal stages. These forms are amenable to anticysticercal treatment. Encysted larvae can remain asymptomatic for years (4,28,30).

• Epilepsy: Patients presenting with parenchymal calcifications (granulonodular stage) can often develop epilepsy (4,32,33).
• Extraparenchymal NCC: Cysts tend to grow irregularly according to the available space, usually around the rostral brainstem or sylvian fissure and usually lack a scolex. They can elicit a strong inflammatory response, especially in the subarachnoid spaces, and the cysts may reach enormous sizes (1,5,12,34).
• Obstructive hydrocephalus: Cysticerci within the ventricular system may narrow or block cerebrospinal fluid (CSF) pathways and the induced inflammation may impair CSF circulation (1,5,12,20,32,33,35).
• Basilar arachnoiditis: This form is seen in patients with subarachnoid NCC. Many patients can have mixed forms (8,12,33).
• Inflammatory response: Larvae-induced inflammatory responses may cause seizures.  The mechanism for this is debatable and likely includes local inflammation and reactive gliotic scars (30,32).
• Cysticercus encephalitis: This can occur when multiple brain cysts degenerate leading to severe brain edema, intracranial hypertension, and even death (12).
• Intradural spinal cysticercosis: This is a rare condition that can be subdivided into leptomeningeal (subarachnoid) or intramedullary (parenchymal) forms, the former being the most prevalent type. The disease may spread by hematogenous (venous or arterial), and CSF flow in the central canal and/or the subarachnoid route. The spinal cord’s central canal, usually open until the 12th year of age, provides a natural pathway into the spinal cord (36).

Histopathology

• Cysticerci microscopic anatomy:  Cysticerci are cystic organisms composed of a complex wall surrounding a cavity that contains vesicular fluid and a scolex.
• Microscopically, the demonstration of the parasite is diagnostic: Along with many calcareous spherules, the scolex, if found, provides definite evidence of the parasitic etiology (36,37).

Cross-section of cysticerci stained with hematoxylin & eosin (H&E), at 40× magnification. The typical finding shows a cysticercus larva enclosed in a cyst wall with three layers (cuticular, cellular, and reticular) and the scolex (arrow)

• Inflammatory process: Inflammation and edema of variable extension are seen in the surrounding tissues and is, in part, dependent on the stage of the process. Severe inflammatory reaction can also be seen in the leptomeninges and ependyma when the cysts are located in the subarachnoid spaces or within the ventricles (8). Occlusion of small vessels in the subarachnoid spaces may result in brain infarction (30,31)
• Involution: The cysticerci in the brain and other tissues undergo a natural process of involution or degeneration over a variable period, ranging from a few weeks to several years. Presenting with a vesicular or colloidal fluid at the beginning (active phases), the scolex disintegrates, and, in the end, the cyst becomes completely calcified, reduced to one third or one fourth of its original size. Although no longer active, it may still be a cause of seizures (25,27,32,33).

CAT scan of multiple degenerated and calcified cysts. These cysts are no longer active but may be the cause of persistent seizures