eMedicine Specialties > Neurology > Neurological Infections

Neuroimaging in Neurocysticercosis

Author: Arturo Carpio, MD, Director of Epilepsy Center, Professor, Department of Neurology, University of Cuenca School of Medicine, Ecuador; Senior Research Scientist of the GH Sergievsky Center, Columbia University
Coauthor(s): Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Contributor Information and Disclosures

Updated: Jul 10, 2009

Introduction

Background

Taeniasis and cysticercosis remain a global public health problem in both the developing and developed countries. Infection is becoming increasingly common in the latter because of the increasing immigration and more frequent travel to regions of endemic disease. These parasitic diseases are related to poverty and poor sanitary infrastructure. Therefore, cysticercosis has been designated as a biological marker of the social and economic development of a community.

Neurocysticercosis (NC) commonly is associated with clinical manifestations such as seizures, headache, and focal neurological deficits, and may lead to long-term neurological sequelae such as epilepsy, hydrocephalus, and dementia. The pleomorphism of NC makes its diagnosis impossible on clinical grounds alone. An accurate diagnosis is possible only after suspicion on epidemiologic grounds, proper interpretation of clinical data, and synthesis of findings on neuroimaging studies specific immunologic tests on the cerebrospinal fluid (CSF).

Biology

Humans are the only known host to harbor the adult cestode parasite, Taenia solium, in the intestine. Infection is acquired by ingesting undercooked pork infected with Taenia larvae (ie, cysticerci). The cysticerci evaginate into the intestines where they mature into adult worms. The worms consist of a scolex, which attaches itself to the intestinal wall, and numerous proglottids (ie, segments). Proglottids and eggs are shed intermittently into the stool.

The intermediate host, typically the pig, is infected by ingesting parasite eggs or proglottids containing eggs (ie, porcine cysticercosis). The oncospheres escape from the eggs, penetrate the intestinal mucosa, migrate through the bloodstream, and lodge in the tissues. Over weeks to months, they evolve into larvae that enlarge and mature into cysticerci. The life cycle is completed when humans ingest pork contaminated with the cysts.

Human cysticercosis is acquired after eating food contaminated with fertilized eggs excreted in the feces of Taenia carriers. In humans, the most common routes of infection are ingestion of T solium eggs from contaminated food and rarely from fecal-oral autoinfestation from patients harboring the adult parasite in their intestines. While the cysts can develop in any human tissue, they have a predilection for the central nervous system (CNS), skeletal muscle, subcutaneous tissue, and eyes.

Immune response

In humans and pigs, the cysticerci may live within the host tissue without causing inflammation or disease. The immune response is unpredictable and may vary from a complete tolerance to an intense immune response. A single patient may show an intense inflammation around a cyst at any stage of the degeneration process, together with viable cysts with lack of inflammation and several calcifications scattered in the brain. Autopsies of victims of warfare and road/traffic accidents have revealed that a large proportion of NC infection is asymptomatic and discovered incidentally at necropsy. Individuals who undergo computed tomography (CT) of the head for unrelated reasons (eg, head injury) may demonstrate multiple parenchymal calcifications.

Several studies have analyzed the mechanisms of the immune response elicited against T solium cysticercus, such as the heterogeneity of the humoral immune response, the existence of immune evasive mechanisms, and the fact that the immune response can both protect and harm the host.

The humoral immune response to antigens of T solium cysticerci is evident from the number of immunodiagnostic assays that have been developed using different types of antigens. Several immunoglobulin (Ig) classes are produced as specific antibodies against the parasite. The most frequent is immunoglobulin G (IgG), which can be detected in serum, CSF, and saliva and suggests that infection is of long duration. The immune response against T solium cysticerci appears to have components of both T helper type 1 cells (Th1) and T helper type 2 cells (Th2), although the underlying mechanisms are yet to be clarified. The parasite is probably killed by eosinophils, which are attracted to the site by lymphoid cells. It is assumed that this specific response is mediated by Th2 cytokines.

Pathophysiology

The natural history of cysticerci in the CNS is not entirely understood. CT scan and magnetic resonance imaging (MRI) have been useful in the study of the evolution of the cysticercus within the brain parenchyma. MRI is more useful than CT scan in detecting intraventricular and subarachnoidal cysts, as well as the accompanying signs of cyst degeneration and pericystic inflammatory reaction. However, CT scan is preferred for detection of parenchymal calcifications.

Once the oncosphere has passed into the parenchyma, it grows and evolves through vesicular, colloidal, nodular-granular, and calcified phases. In the vesicular phase, the host tends to show immune tolerance, and, in most cases, no surrounding parenchymal reaction occurs. The larva lives inside a translucent liquid-filled cystic structure surrounded by a thin membrane, where it can remain viable from a few months to several years. When the larva is viable, the CT scan depicts circumscribed, rounded, hypodense areas, varying in size and number, without enhancement by contrast medium (Media files 1-2). The average size of the cysts is 10 mm in diameter, but they range from 4-20 mm.

On MRI, the vesicular larva appears as CSF-like intensity signal on all sequences (Media file 1), with no surrounding high signal on T2-weighted images. Both MRI and CT scan may show a high intensity, 2-4 mm mural nodule, depicting the scolex in the interior of some parenchymal vesicular cysts (Media file 1). This picture could be considered pathognomonic of cysticercosis, and it corresponds to the active parenchymal form of NC. Two phases of pathologic changes take place when the host-immune system reacts to the parasite.

Colloidal phase

In this phase, the parasite begins to show degenerative changes, the vesicular fluid takes on a gelatinous colloidal aspect, and the wall thickens. The contrast-enhanced CT scan shows an annular enhancement surrounded by irregular perilesional edema. On MRI, the capsule shows higher signal than the adjacent brain with thick-ring enhancement on T1-weighted images, while on T2-weighted images a low-ring signal surrounded by high signal lesion is seen (Media files 1-2).

Nodular-granular phase

In this phase, the vesicle tends to shrink, and its contents become semisolid, being progressively replaced by granulomatous tissue. These findings could correspond to a diffuse hypodense area with irregular borders on noncontrast CT scan. Following administration of contrast medium, a small, hyperdense, rounded, nodular image surrounded by edema is observed (Media files 2-3). In this stage, T2-weighted images depict the most striking picture of these lesions, as they show a change in the signal from the cyst fluid.

These 2 consecutive phases correspond to an intermediate stage named transitional form, inasmuch as the cysticercus has entered into a degenerative process. Although these pathologic changes generally are associated with symptoms (eg, seizures, headaches), some patients with these changes remain asymptomatic. The cysts in the transitional phase may be single or multiple. If multiple, and coexisting with other cysts in the vesicular phase and disseminated calcified nodules in the cerebral parenchyma, the most likely diagnosis is NC (Media file 1). However, when only one cyst is seen in the transitional phase, it corresponds to the so-called "single enhancing lesion on CT" (SECTL) (Media files 2-3), signifying a special syndrome.

When the parasite dies, a mineralization and resorption process occurs that ends in a calcified nodule that lodges permanently in the CNS. Noncontrast CT scan shows a rounded, homogeneous hyperdense area showing no enhancement with contrast medium (Media files 1-2). This phase corresponds to the inactive parenchymal form of NC.

The parasite in the active stage may remain viable from a few months to several years. The transitional stage may last about 3-12 months or longer, usually 4-6 months. Finally, the dead parasite is reabsorbed, or it calcifies and lodges permanently in the CNS.

A NC form with different clinical and radiologic characteristics from those already described is termed "cysticercotic encephalitis." It occurs primarily in children and young women. The noncontrast CT image shows diffuse and intense cerebral edema and small or collapsed ventricles. Contrast-enhanced images show multiple, small, hyperdense, nodular or annular images disseminated throughout the whole cerebral parenchyma (Media file 4).

When the parasites are located in the subarachnoidal space or inside the ventricular system, the clinical course also varies from the typical presentation. Being immersed in a CSF-rich environment, the cysticerci evolve into the racemose form of NC.

Racemose form

The racemose form constitutes a hydropic change that leads to large or even giant vesicles usually devoid of a scolex. These racemose cysts show a rapid process of hyalinization of the cyst wall. They are located most frequently either in the basal cisterns or inside the sylvian valley, and they can be as large as 100 mm in diameter. Noncontrast CT scans depict hypodense images in the subarachnoid or ventricular space. The cysts deform the surrounding structures, and a noncommunicating hydrocephalus occurs.

MRI shows the cyst more precisely as a hypointense CSF-like image in all the phases (proton or T2 weighted). It permits direct visualization of the intraventricular cysticerci by identifying the cyst wall, scolex, or both. The ventricular ependymal lining reacts to the cysts and an inflammatory reaction or ependymitis occurs, which can be visualized on CT scan or MRI as a high-intensity signal in the ependymal layer. When the parasite is located in the subarachnoid space, it can cause a meningeal inflammatory process, with pleocytosis and increased protein in the CSF. The parasite degenerates to a hyaline mass and remains trapped inside the gummatous thickening of the leptomeninges. As a sequel to the chronic intense inflammatory process, fibrosis and thickening of the leptomeninges also may lead to chronic hydrocephalus. Vasculitis with secondary ischemic lesions may be noted.

Classification of NC

Carpio proposed an improved and widely accepted classification system based on the viability and location of the parasite in the host CNS.

• Active, when the parasite is alive
• Transitional, if it is in the degenerative phase
• Inactive, if evidence of its death is apparent

Each viability category is subdivided into parenchymal and extraparenchymal forms. On the basis of this classification, relating clinical manifestations to each category of the proposed classification is possible. No definitive data exist regarding the duration of individual stages. Anecdotal evidence indicates that, once the parasite lodges in the brain, it may remain viable from months to years. The transitional phase lasts 4-6 months. Finally, the dead parasite is resorbed or it calcifies and lodges permanently in the CNS.

Frequency

United States

Traditionally NC has been considered an exotic disease in the United States. This infection now accounts for as many as 2% of neurologic and neurosurgical admissions in southern California. More than 1000 cases are reported per year in the United States. Persons who have never left the United States are at risk as well as visitors to disease-endemic regions. An outbreak of cysticercosis among orthodox Jews living in New York City was reported after food was contaminated with T solium eggs by immigrant cooks infected with the pork tapeworm. The Centers for Disease Control and Prevention (CDC) considers NC an emerging infection, and they are developing programs to track and hopefully eradicate the condition.

International

NC is the most common neurological infection in the world. NC is endemic in much of the developing world. Most publications on the frequency of NC are based either on autopsy or biopsy materials or on data culled from neurologic settings and general hospitals. These data are hardly representative of the general population.

T solium is endemic in Latin America, India, and China, and it also may be endemic in sub-Saharan Africa. In countries where the disease is endemic, NC is also widely prevalent in the urban middle class areas.

Epidemiological surveys for human cysticercosis, using immunoserologic assays, such as the enzyme-linked immunoelectrotransfer blot assay (EITB) or the enzyme-linked immunosorbent assay (ELISA) have been explored. These assays are useful for identification of individuals who have had systemic contact with the parasite at some time. However, seropositivity does not necessarily mean an active systemic infection or CNS involvement at any time.

EITB assays report a seroprevalence from 8-12% in some regions of Latin America. Most seropositive individuals in these populations are asymptomatic. No prospective studies provide information on the proportion of seropositive individuals that will develop seizures or other neurological symptoms. Some studies, but not all, have reported an association between seizures and seropositivity. Although a higher proportion of patients with epilepsy have been shown to be EITB positive when compared to those without epilepsy, the proportion of seropositivity in epileptic patients is similar to that reported in the general population in these same areas.

Recent epidemiological studies have shown that persons engaged in household contacts with patients with NC had a risk of positive serology for cysticercosis that was 3 times higher than the general population. While these findings are still consistent with a common environmental source of infection with T solium eggs, they also suggest a potential for direct human-to-human contamination.

Mortality/Morbidity

No reliable information is available regarding mortality rates. This is probably because a large percentage of patients (perhaps as many as 50%) with NC are asymptomatic. Most patients with parenchymal NC have a benign clinical cause. However, patients with subarachnoidal cysticercosis (approximately 10-15%, including intraventricular cysts) may develop complications such as vasculitis and hydrocephalus.

• Permanent neurological deficits may result secondary to infarction in the case of vasculitis, and high mortality rates or severe clinical morbidity such as dementia may result from hydrocephalus.
• Hydrocephalus has been reported as a complication (8%) of treatment of NC with albendazole or praziquantel.
• Anecdotal reports have circulated concerning patients with intraventricular cysts who experienced sudden death due to acute obstruction of the intraventricular system, particularly the aqueduct of Sylvius.

Race

No racial risks or protection are known in cestode infestation.

Sex

Men and women are affected similarly. However, cysticercotic encephalitis, one of the most severe forms of NC, is seen more frequently in young women than in men.

Age

• NC has been reported in all age groups. The most frequent presentation occurs in the third and fourth decades of life.
• Reports of cysticercosis are very unlikely in children younger than 2 years of age because of the prolonged incubation period of T solium. Most often, the disease is recognized in children older than 7, due to this incubation period.
• The clinical course of NC in children is usually benign and self-limited and the prognosis good.

Clinical

History

• Neurocysticercosis (NC) is frequently asymptomatic. Cysticercosis of other tissues is almost always asymptomatic.
• Clinical manifestations of NC are variable and dependent on the number and location of cysts as well as the host-immune response to the parasite.
• The most frequent clinical manifestations are the following:
  • Seizures
  • Intracranial hypertension
  • Focal neurological deficits
  • Mental changes
• A myriad of syndromes have been described, including brainstem dysfunction, cerebellar ataxia, sensory deficits, involuntary movements, stroke, dementia, and hydrocephalus.
• A survey carried out in Mexico on 205 patients with NC (114 adults and 92 children younger than age 15 y) who were diagnosed by means of neuroimaging reported that seizures were more frequent in children (80% vs 56%), while headache was more frequent in the adults (27% vs 15%).³⁶
• Ten percent of patients present with ventricular cysts, with seizures, or with meningeal inflammation.
• Symptoms include nausea, vomiting, headache, ataxia, and confusion.
• Most of these clinical manifestations develop over a period of a few days, weeks, or months, with periods of remission and relapse, probably due to different evolutionary stages of the parasite.

Physical

• No pathognomonic physical findings unmistakably identify a patient with NC. Virtually any neurological sign or symptom can occur, depending on the CNS location of the parasite.
• Patients with cysts in the basal cisterns can present with meningeal signs, hydrocephalus, vasculitis, and stroke.
• Cysticercal encephalitis with multiple parenchymal cysts (ie, associated inflammatory response, diffuse cerebral edema) is a rare presentation often seen in young girls. These patients are at a risk of developing severe neurological sequelae.
• In patients with seizures, SECTL or hyperintense lesions on MRI are a common finding. The lesion is usually small, about 5-10 mm, well defined, annular or nodular, contrast enhancing, cortical or subcortical, and generally associated with perilesional edema and minimal mass effect, but without midline shift (Media file 3). These patients, mainly children and young adults, have some benign and transitory clinical manifestations, predominantly partial or partial secondary generalized seizures, and occasionally Todd paresis or focal neurological deficits.

Causes

• Risk factors associated with the disease include the following:
  • Immigration from areas of endemic disease
  • Family history of parasitic infestation
  • Household visitors from an endemic area
  • History of travel to an endemic area
• Other diagnostic considerations
  • Focal signs may occur abruptly in patients who develop a cerebral infarction as a complication of subarachnoid NC.
  • Some manifestations of spinal NC are nonspecific, and the differential diagnosis with other diseases of the spinal cord is difficult on clinical grounds.
  • Arachnoiditis is characterized by root pain and weakness of subacute onset. Cysts in the spinal cord parenchyma usually occur with motor and sensory deficits that vary according to the level of the lesion.
  • Diffuse muscle involvement may result in a pseudohypertrophic myopathy. Patients have diffuse swelling of the muscles mimicking hypertrophy, myalgia, and muscle weakness.

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