Neurocysticercosis (Cysticercosis)

Neurocysticercosis[1]

Neurocysticercosis (NCC) is an infection of central nervous system caused by larva of the tapeworm Taenia solium (pork tapeworm).

The disorder is the result of this process: infectious.

Presentation

Depending upon number, location and stage of cysticerci (viable, degenerating or involuted/calcified), presenting symptoms can be particularly varied. Inflammatory response of host also determines the severity of signs and symptoms. Cysticerci, that are located on cerebral convexity, are usually small, while some, for example those in area of Sylvian fissure may approach to large sizes (sometimes 50mm), displace surrounding structures, form space occupying lesions in brain and present with severe epilepsy, hydrocephalus or other symptoms. These lesions are often multilobulated. One unique form of disease, called racemose neurocysticercosis, appears macroscopically as branches of grapes that are actually clusters of cysticerci formed close to each other, commonly located in sub-arachnoid space. One important hallmark of neurocysticercosis is the presence of viable, degenerating and calcified cysts at the same time in brain. These cysts may be asymptomatic or they may be showing an inflammatory response.

Parenchymal neurocysticercosis presents with epilepsy/seizures, which is the most common manifestation present in 70-90% of cases. Seizures are usually of abrupt onset. Extraparenchymal neurocysticercosis causes hydrocephalus. Fibrous arachnoiditis is most common finding in subarachnoid neurocysticercosis.

Rarely, patients with neurocysticercosis present with intracranial hypertension, chronic meningitis and cranial nerve abnormalities. These are abnormal findings and they depend upon location of cysts in central nervous system. Cysts may also occur in spine or eye. Neurological deficits may occur due to stroke, cerebral infarcts are common in the parenchymal form of the disease. Headache is another common feature, which is chronic in some cases. Psychiatric symptoms include depression and psychosis [8] [9]. Except for seizures, most of these symptoms are subacute or chronic in nature.

Apart from these classical signs and symptoms, patient can come up with hemiplegia, hemiparesis, sensory loss, diplopia or other manifestations of extraocular muscle paralysis, dysarthria and movement disorders, mainly depending upon cyst location. Vasculitis is another uncommon finding. Cognitive decline and meningeal signs (drowsiness, neck rigidity, nausea, headache and vomiting) may be present.

Complications can occur in the form of:

  • Chronic epilepsy (most frequent complication)
  • Neurological deficits 
  • Hydrocephalus, rarely causing herniation
  • Chronic meningitis

Workup

A detailed history must be taken from patient regarding residence, recent travels to high risk areas or any close contact with a suspected carrier. Neurocysticercosis is diagnosed by routine imaging techniques, computed tomography (CT) and magnetic resonance imaging (MRI). In very rare and extreme cases, biopsy of the brain is taken in order to make a diagnosis. Serological tests against cyst antigen are also done. Cysticerci may also be present in other parts of the body and discovery of these extra-neural cysts strongly supports the diagnosis.

MRI is a standard procedure, and non-invasive magnetic resonance procedures like magnetic resonance cisternography (MRC) or fluid-attenuated inversion recovery (FLAIR) may also be used. CT scan alone, can detect hydrocephalus in cases of extraparenchymal neurocysticercosis and fibrous arachdoinitis [5] [10]. However, cysticerci in basilar turns are difficult to visulaize through CT. Leptomeningial enhancement at base of brain requires MRI for a better visualization [11].

Generally, parenchymal neurocysticercosis presents with complications that are indistinguishable from cerebral infarcts. Such infarcts must be considered while making a diagnosis. Biopsy, that is rarely used, is an invasive procedure. Hence, it is not done unless other diagnostic facilities fails and patient is unresponsive to treatment. Recommendation of prior anti-cysticercal drug treatment and brain imaging is made before considering biopsy.

Racemose form of disease can be better diagnosed with non-invasive magnetic imaging techniques, for example MRC and FLAIR sequences before and after inhalation of 100% oxygen. Lab results often show eosinophilia, elevated erythrocyte sedimentation rate and leukocytosis on routine investigations. Psychiatrists must keep in mind a diagnosis of neurocystercosis in patients of deprssion and psychosis, as recent studies show that patients visiting a psychiatric outpatient department are more likely to have positive serology for Taenia solium than healthy individuals in community.

Treatment

Neurocysticercosis-associated epilepsy is an important cause of neurologic morbidity [11]. Despite recent advances, treatments remain either suboptimal or based on poorly controlled or anecdotal experiences [1].

Patients with smaller number of cysts show excellent prognosis, sometimes without antihelminthic therapy. Others require antihelminthic/antiparasitic drug (for example albendazole) and other medical interventions or surgical treatment. Treatment depends upon the viability of cyst and its complications [12].

Treatment goal is to manage neurological and other symptoms in patients and elimination of cysticerci in brain [13].

Management of symptoms

Antiepileptic drugs are used in case of patients presenting with seizures. Some patients require only first line antiepileptic drugs. Most commonly phenytoin and carbamazepine are used by patients. With advancement in pharmaceutics, newer and better drugs have been introduced but they have net yet gained much popularity because of higher cost [14], although, control of seizure may be gained almost as much effectively through these newer agents and they also carry lesser risk of withdrawal symptoms.

Patients presenting with hydrocephalus may require placement of ventricular shunt. Steroids are also made a part of medical treatment to control damaging and potentially harmful host inflammatory responses.

Elimination of cysticerci

Surgery is mostly restricted to shunt placement or removal of cysts. If hydrocephalus is being presented because of fibrous arachnoiditis, a ventricular shunt is planted, and medical treatment given afterwards. Ventricular shunts are also placed in other patients presenting with hydrocephalus in any other form of extraparenchymal neurocysticercosis, followed by surgical removal of cysts and medical treatment [15]. As compared to Pudenz-type shunt that use valve type mechanism and is associated with shunt dysfunction, Sotelo has designed a shunt that maintains a constant flow without valvular mechanism. This prevents shunt dysfunction caused by entry of inflammatory tissue and parasitic debris in brain cavities.

In case of multiple symptoms, persistence/increase in severity of symptoms, surgery is performed in order to extirpate cysticerci. Patients who harbor large number of cysts in their brain, must be treated with surgical extirpation on an urgent basis. Patients, in which the number of cysts is small may not require surgery. Surgery is also indicated in patients who do not respond to medical treatment or in those who present with ocular or spinal lesions. Racemose form of disease and any extraparenchymal form of disease causing hydrocephalus also requires surgical extirpation of cysts.

Frequently, patients develop complications due to medical and surgical therapy. Care must be taken while prescribing antihelminthic drugs because degenerating cysts can cause an intense inflammatory reaction in brain, that mimics natural evolution of cysts. This may increase symptoms, or even cause death.

Prognosis

No figures are available to precisely describe mortality and morbidity associated with neurocysticercosis. Once diagnosed, neurocysticercosis in most patients, shows good prognosis. However, some patients may get complications from medical or surgical therapy. There is no specific duration for medical treatment. Patient may recover after use of antihelminthic drug, where as some refractory patients develop chronic epilepsy.

Differentiation between parenchymal and extraparenchymal form of the disease is important. Parenchymal disease is associated with better prognosis than the extraparenchymal form. Symptoms of the parenchymal form, like seizures, may improve after antihelminthic drug treatment, for example with albendazole. However, these drugs may cause an inflammatory response in brain, and hence, their use must be carefully prescribed. In some fortunate cases, symptoms resolve without any medical or surgical treatment. Once the disease is controlled, seizures can be treated by first line anti-epileptic drugs e.g, carbamazepine.

Prognosis in extraparenchymal form is not as good as in other form of disease. Anthelmintic treatment may induce regression of the cysts, which, in contrast to parenchymal cysts, frequently require long-term and multiple courses of anthelmintics [1]. 

Racemose neurocysticercosis, a unique form of disease, is associated with poor prognosis (higher morbidity and >20% elevated mortality rate) [7]. Patients with complications e.g, hydrocephalus, stroke, vasculitis, etc., also do not well. Total number of cysts in brain largely determines the disease outcome. A high parasitic load (>50 cysts) can cause severe symptoms and hence, grater morbidity and mortality.

Etiology

Tapeworm infection is known as taeniasis. Its most important clinical manifestation is the formation of cysts in central nervous system, called neurocyticercosis. Neurocysticercosis develops when humans accidentally ingest worm (Taenia solium) eggs through contaminated water or food. Contamination occurs when eggs or gravid proglottids (segments of parasite containing formed eggs) of the parasite enter environment. Adult tapeworm, that resides inside the small intestine of a carrier, releases eggs which come out through feces.

Most commonly, the risk factor for infection is the proximity of a carrier of tapeworm [1] [2]. Infection occurs through fecal-oral contact that indicates the presence of a carrier in immediate environment. Note that humans are definitive hosts of Taenia solium, while pigs are intermediate hosts. A definitive host is one in which the adult form of parasite lives and takes nutrition from, while on the other hand, intermediate stages of life cycle of the parasite (like cysticerci in pigs muscle) dwell in an intermediate host.

Another interesting mode of infection in neurocysticercosis is autoinfection, in which the person gets infected with eggs of a worm that resides in his own intestine. In such cases, there is prior ingestion of poorly cooked or raw pork meat by the person, that contains larva or cysticerci (but not eggs). The cysticerci evaginate in small intestine where they get attached to the gut wall with the help of the scolex (head of parasite that contains suckers and hooks). It takes nutrition and develops chain of proglottids (called strobila, body of parasite without head) and increases in length. Fertile eggs are released into gravid proglottis. A single proglottid can contain about 60,000 eggs. Proglottids containing eggs are detached and released and subsequent contamination occurs.

Epidemiology

Taenia solium infections occur worldwide but incidence rates are highest in Asia, Sub-Saharan Africa and Latin America. In the US, taeniasis or cysticercosis is detected in immigrants from these high risk areas. Immigrants from Mexico, Guatemala and other Latin American countries, where poor sanitation and unhygienic conditions are predisposing factors, bear a higher risk of disease. New cases of neurocysticercosis arise from fecal-oral contact of healthy individuals with carriers.

Sex distribution
Age distribution

Pathophysiology

Cysticerci are encysted larvae of the parasite. The cysts can form inside the parenchyma of the brain or outside it, hence neurocysticercosis is classified into parenchymal and extraparenchymal neurocystcercosis. 

After ingestion, embryos are released from eggs in small intestine. The larvae enter the circulation and, through blood, reach to various organs. Note that, in humans, it is not only brain tissue that is the site for cyst formation, rather cysts can form in skeletal muscle, eyes, skin or even cardiac muscles of patient (the most common site for cyst formation is skeletal muscle). The subsequent symptoms and complications, however differ depending upon tissues involved. After reaching brain parenchyma, larva get encysted to form cysticerci. These cysticerci are of various sizes, some forming large space occupying lesions in brain. 

Cysticerci pass through a sequence of changes in nervous tissue. These are the stages of involution of cyst [3], as a viable cyst is gradually converted into a coarse calcified nodule. Each stage has its own diagnostic feature and inflammatory response invoked by each is different. The first stage is vesicular stage, in which a cysticercus resembles a fluid filled translucent bladder. It is hypodense and invokes little inflammatory response at this stage. The cyst, at this point has an invaginated scolex and is filled with fluid. In the next stage, the fluid turns less translucent, scolex degenerates and walls also get thicker. This stage is called colloidal stage. It appears as a hypodense structure with enhancement in contrast CT and MRI. At this stage, fluid leaks in surrounding parenchyma and invokes an intense inflammatory response from the host immune system [4]. Leaked fluid and inflammatory response, together, produce edema around the cyst that is responsible for enhancement that appears in radiographic examinations [5]. In the next stage, the granular stage, degeneration starts, scolex reduces and walls become thicker. Gliosis also develops at this stage. The last stage is the calcific stage in which cysticercus transforms into a calcific nodule which appears hyperdense in imaging techniques [6]. Seizures, the most common manifestation of neurocysticercosis, generally occur in viable and degenerating stage of cyst in which the body shows vigorous inflammatory response to larval parasite. In extraparenchymal neurocysticercosis, cysts (which may be multiple in number at a site) can cause obstruction, which leads to an increase in intracranial pressure.

Prevention

Incidence and prevalence of the disease can be reduced by appropriate prevention, screening of carriers and treatment of all those who have been infected with parasite. Fecal-oral transmission of eggs from persons with taeniasis must be prevented in order to break the chain of transmission of parasite.

Screening must be carried out in close contacts of those in whom disease is diagnosed. Identification of carriers is an important measure in prevention of this disease. A longitudinal study at Los Angeles County Health Department showed that family contacts of cases were frequently the carriers of tapeworm. Food handlers should be educated in good handwashing practices and other hygienic measures. CDC does not recommend routine testing of food handlers for taeniasis, but recommends stool examinations in immigrant employees that are found to be in close contact of any new case. While traveling abroad to high risk areas, care must be taken to avoid any food article that might be carrying the risk of contamination.

Summary

Neurocysticercosis (NCC) is caused by formation of larval cysts of the parasite Taenia solium in the central nervous system. Neurocysticercosis is primarily classified into two types; parenchymal and extraparenchymal neurocysticercosis. This disease is more common in developing countries. In developed countries like the United States, it is mainly a disease of immigrants. Degenerating cysts in brain invoke an inflammatory response. Main manifestations are seizures and hydrocephalus. Treatment includes medical therapy (for seizures, inflammation, helminth elimination etc.) and surgical interventions, in order to extirpate the cysts.

Patient Information

Neurocysticercosis is caused by the larval form of parasitic tapeworm Taenia solium. Infection is usually acquired by ingestion of food or water contaminated with worm eggs. The larva of the worm form numerous cysts in brain. A viable cyst generally does not cause any symptoms in body. Rather, symptoms appear in patient when these cysts degenerate.

Neurocysticercosis is classified into two types, parenchymal or extraparenchymal cysticercosis, depending upon the location of cysts in brain. Neurocysticercosis may preset with seizures/ epilepsy or a raised intracranial pressure. Diagnosis is made through serology, CT, MRI and other brain imaging techniques. Sometimes, a biopsy may be required in rare cases.

Treatment is through antihelminthic, anti-epilepsy, and anti-inflammatory drugs and surgery. Prevention can be achieved through good hand washing practices and avoidance of food likely to be contaminated with tapeworm eggs.

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References

  1. Nash TE, Singh G, White AC, et al. Treatment of neurocysticercosis: current status and future research needs. Neurology 2006; vol. 67, no. 7, pp. 1120–1127.
  2. Lescano AG, Garcia HH, Gilman RH, et al. Taenia solium cysticercosis hotspots surrounding tapeworm carriers: clustering on human seroprevalence but not on seizures. PLoS Neglected Tropical Diseases 2009; vol. 3, article e371.
  3. Escobar A, Palacios E, Rodriquez-Carbajal J, Taveras JM, eds. The pathology of neurocysticercosis in Cysticercosis of the Central Nervous System. Charles C. Thomas, Springfield, Ill, USA 1983; pp. 27–54.
  4. Del Brutto OH, Sotelo J, and Roman G. Neurocysticercosis: A Clinical Handbook, Swets & Zeitlinger, Lisse, The Netherlands, 1998.
  5. Garcia HH, Del Brutto OH. Imaging findings in neurocysticercosis. Acta Tropica 2003; vol. 87, no. 1, pp. 71–78.
  6. Del Brutto OH. Neurocysticercosis. Seminars in Neurology 2005; vol. 25, no. 3, pp. 243–251.
  7. Bickerstaff ER, Cloake PC, Hughes B, Smith WT. The racemose form of cerebral cysticercosis. Brain. 1952 Mar. 75(1):1-18.
  8. Forlenza OV, Filho AH, Nobrega JP, et al. Psychiatric manifestations of neurocysticercosis: a study of 38 patients from a neurology clinic in Brazil. Journal of Neurology, Neurosurgery and Psychiatry 1997; vol. 62, no. 6, pp. 612–616.
  9. Bandres JC, White AC Jr., Samo T, Murphy EC, Harris RL. Extraparenchymal neurocysticercosis: report of five cases and review of management. Clinical Infectious Diseases 1992; vol. 15, no. 5, pp. 799–811.
  10. Martinez HR, Rangel-Guerra R, Elizondo G, et al. MR imaging in neurocysticercosis: a study of 56 cases. American Journal of Neuroradiology 1989; vol. 10, no. 5, pp. 1011–1019.
  11. Del Brutto OH. Cysticercosis and cerebrovascular disease: a review, Journal of Neurology. Neurosurgery and Psychiatry 1992; vol. 55, no. 4, pp. 252–254.
  12. Garg RK. Treatment of neurocysticercosis: is it beneficial?. Expert Rev Anti Infect Ther. 2008 Aug. 6(4):435-40.
  13. Kaushal S, Rani A, Chopra SC, Singh G. Safety and efficacy of clobazam versus phenytoin-sodium in the antiepileptic drug treatment of solitary cysticercus granulomas. Neurol India 2006; 54:157.
  14. Rangel-Castilla L, Serpa JA, Gopinath SP, Graviss EA, Diaz-Marchan P, White AC Jr. Contemporary neurosurgical approaches to neurocysticercosis. Am J Trop Med Hyg. 2009 Mar. 80(3):373-8.
  15. White AC Jr, Weller PF. Cestodes. Kasper DL, Braunwald E, Hauser S, et al, eds. Harrison’s Principles of Internal Medicine. 16th ed. New York, NY: McGraw-Hill; 2004. Chapter 204.

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Media References

  1. Neurocysticercosis, Public Domain

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