Management of Neurocysticercosis

Epidemiology

The incidence of NCC varies among different continents; however, it is the most frequent parasitic disease that affects the CNS. It is endemic in countries of Africa, Central and South America, and in Southeast Asian countries. Symptoms of the disease can present between 2 months and 30 years after the initial infection.

Subcutaneous nodules may be present in infected patients. However, the extraneural form of this disease usually has a benign course. Involvement of the CNS is generally a consequence of cerebral pathology, with a lesser involvement of the spine. Neurologic implications of this disease are relevant; NCC is the cause of 12% of hospitalizations and the most common cause of acquired or late onset epilepsy in countries of Latin America. ^, Patients suffer severe neurologic complications at a productive age. Further, it is considered that more than 50,000 deaths worldwide are related to NCC, making this disease a large public health issue. ^,

Parasitic Life Cycle

The etiologic agent of cysticercosis is the T. solium at its larval stage, the c ysticercus cellulosae . T. solium has a two-host complex life cycle. The human is the definitive host for the adult and the pig is the intermediate host for the larval cysticercus. However, the human can also serve as the intermediate host after ingestion of T. solium eggs. ^,

Humans become infected with tapeworm after ingesting pork meat containing cysticerci, the larval form of the parasite in the first stage of infection. In the small intestine, the scolex evaginates and attaches to the mucosa where it grows into the adult form of the tapeworm in the second stage; humans develop intestinal teniasis. The adult tapeworm is hermaphrodite and has multiple segments, each containing a branched uterus laden with infective eggs called proglottids, which it sheds into the fecal matter approximately 4 months after attachment during the third stage of infection. The adult tapeworm can live up to 25 years. They remain viable several weeks in contaminated soil after excretion. The eggs are disseminated in the environment and are later ingested by pigs and humans. This entails fecal–oral transmission of infective eggs to humans as autoinfection or transmission to other individuals. Another possible but unlikely mechanism of development of cysticercosis is by retrograde peristalsis with the subsequent penetration of the mucosa by the larvae ( Fig. 131.1 ). All of these mechanisms are due to poor hygienic measures, for example, lack of handwashing before meals and after defecation, or contamination of water or food with feces of carriers of the adult tapeworm.

A high proportion of tapeworm carriers as well as their family members develop cysticercosis after ingestion of the infective eggs. ^, In the intestine, the egg becomes the oncosphere . When the oncosphere hatches, it penetrates the intestinal mucosa and enters the local lymphatic and mesenteric vessels of the intermediary host; it then develops into the cysticercus in the hosts muscle, usually the pig, which is then ingested by the human and develops into intestinal taeniasis. It lodges mainly in subcutaneous tissue, the brain, and muscle. The fifth stage is the post-oncospheral form, which is followed by the sixth and last stage, the cysticerci, which gives the clinical manifestations according to the tissue and location of their implantation. ^, Neurocysticercosis occurs when the human becomes the intermediary host after ingesting eggs or proglotids. The parasite then enters the human intestinal mucosa and implants into different tissue, such as the muscle and the brain, leading to neurocysticercosis.

Cysticerci are vesicles with two main parts: the vesicular wall and the scolex. The scolex has a similar structure to the adult form of T. solium . This is an armed rostellum and a body. They usually lodge in anatomical sites with abundant vascular supply, that is the cortex or basal ganglia. The macroscopic view of cisticerci varies according to their location in the CNS. For example, in the brain parenchyma the cysticercus measures approximately 10 mm, but in the subarachnoid space, they can grow up to 50 mm. Meningeal cysts adhere to the pia-mater or float freely, particularly in the Sylvian fissure. With time, cysticerci tend to shrink, and the meninges become thickened and fibrotic. Some cysts appear as a grapelike form, attached to each other by several membranes giving rise to the racemose form of the disease. Racemose cysticercosis consists of a large multiloculated mass of cysticerci that lack an invaginated scolex. They are usually in the basilar cisterns and the fourth ventricle. In ventricular cysticercosis, a single cyst is found adhering to the ependymal wall or the choroid plexus; however, it is possible to see them floating in the cerebrospinal fluid.

Pathogenesis and Microscopic Appearance

In the CNS, cysticerci induce an inflammatory response in the surrounding tissues. Initially, in the vesicular stage of the cysticercus, it is associated with a minimal inflammatory reaction; it has a transparent membrane, clear fluid inside, and integrity of the larva and scolex. In the colloidal stage , the cyst shows degenerative changes due to factors like inflammatory reaction and pharmacological therapy. When the disease is in the colloidal stage, the scolex is lost and inflammatory cells, mainly mononuclear/macrophages, penetrate into the cyst. In this stage the fluid becomes turbid and viscous. Later, in the nodular stage, the cyst is enclosed by a zone of granulation tissue with a dense capsule of collagen, which shows astrocytic gliosis, microglial proliferation and activation, edema, perivascular cuffing and presence of necrotic tissue and cholesterol clefts. Old nodules may be fibrotic and sometimes become mineralized (calcifications). Ventricular cysticerci usually cause granular ependymitis, especially with high doses of cysticidal treatment. Degeneration of racemose cysticerci may cause a granulomatous inflammatory reaction in the subarachnoid space with accumulation of collagen, lymphocytes, multinuclead giant cell, eosinophils, and hyalinized parasitic membranes that have as a consequence leptomeningitis, chronic basilar arachnoiditis, opto-chiasmal arachnoiditis, or hydrocephalus. These inflammatory detritus have as a consequence a decrease in the CSF absorption capacity causing hydrocephalus. Endoscopically, it is possible to visualize an inflammatory reaction in the choroid plexus and ventricular wall in ventricular cysticercosis. Microscopically, it is possible to identify a disrupted ependymal lining, which is replaced by subependymal glial cells. This is an important cause of CSF blockage in narrow spaces such as the cerebral aqueduct and interventricular foramina.

Meningeal and small cerebral arteries show vasculitis with fibroblastic or collagenous thickening of the intima and local excrescences, which may narrow the arterial lumen. The media shows fibrosis, and the adventitia shows infiltration by plasma cells.

Microscopically, the parasite has a scolex has a rostellum provided with four suckers and a double row of 22 to 32 hooklets. The cystic wall consists of three different layers ( Fig. 131.2 ):

• 1.

  The external layer (cuticular) is 3 μm thick, eosinophilic, and has hair-like protrusions called microtrichia.

• 2.

  The middle (cellular) layer.

• 3.

  The inner reticular layer (fibrillary), which may contain mineral concretions.

Initially the parasite is able to evade the host’s immune response by secreting humoral factors that inhibit activation of complement and lymphocytes, the secretion of cytokines, and also secrete prostaglandins that decrease inflammation and manipulate the immune reaction activating the production of T helper 2 molecules. The cysticercus secretes proteases that cleave interleukins and structural components in its wall that inhibit complement activation. On the other hand, patients with acquired immune deficiency syndrome (AIDS) respond differently to the parasite. It has been reported that the incidence of NCC in patients with AIDS has increased, while other reports have found that there is no predisposition of these patients to have NCC suggesting that humoral immunity is more relevant to combat NCC than cellular immunity.

Deposits of immunoglobulin (Ig) E and IgG have been found surrounding cysticerci. Moreover, there are numerous reports of patients that have lesions at different stages, suggesting that the immune reaction against these parasites is heterogeneous and presenting the possibility of re-infection. ^{, ,}