| Neurocysticercosis |
Neurocysticercosis (NCC) is a parasitic infection of the nervous system caused by the tapeworm Taenia solium, also known as the "pork tapeworm". The disease is often caused by eating improperly cooked food or water contaminated with tapeworm larvae (cysticerci). When cysticerci enter the small intestine, they attach to the intestinal wall and grow into a tapeworm. This tapeworm can travel to the brain, muscles, eyes, and skin. Neurocysticercosis manifests with various signs and symptoms, influenced by the location, number of lesions, and immune response, ranging from asymptomatic to fatal; common symptoms included seizures, intracranial hypertension, cognitive impairment, and focal deficits.
Diagnosis relies on neuroimaging and serology. Neurocysticercosis can be prevented through improved sanitation, education, awareness, de-worming and vaccines for endemic areas.
Neurocysticercosis requires a tailored treatment based on cyst viability, the host's immune response, and the location and number of lesions. Symptoms are treated with antiepileptic, antiedema, analgesic, or anti-inflammatory drugs. Surgery, steroids, or other medications are used to treat intracranial hypertension. Anti-parasitic medications are used for treating earlier stages of the disease. Steroids are used to manage inflammation in the central nervous system. Surgery can be used to remove cysts.
Neurocysticercosis is endemic in developing countries, such as Latin America, China, Nepal, Africa, India, and Southeast Asia. Although rare in Europe and the US, immigration has increased its prevalence. Taenia solium has been recognized since 1500 BC and found in ancient Egyptian mummies. The first recorded cases of neurocysticercosis were likely in 1558. In 1792, a Peruvian physician reported simultaneous taeniasis, tapeworm infection in the intestines, and cysticercosis in the same individual. In the 19th century, German pathologists found similarities between T. solium and cysticercus scolex and discovered that consumption of cysticercus in pork caused human intestinal taeniasis.
Neurocysticercosis has a wide range of signs and symptoms. This range of symptoms is due to the location, number of lesions, and immune system's response to the infection. Neurocysticercosis can range from asymptomatic to deadly; it has been referred to as the "great imitator" because it can mimic many other neurological disorders. The most common symptoms of neurocysticercosis are seizures, intracranial hypertension, cognitive impairment, and focal deficits.
| Location | Form of the disease | Common clinical manifestations |
|---|---|---|
| Brain parenchyma | Vesicular cysts | Seizures; sometimes asymptomatic. |
| Colloidal cysts | Seizures; vomiting; headache; focal signs. | |
| Granulomas/calcifications | Seizures, sometimes reoccurring. | |
| Cysticercotic encephalitis | Seizures; coma; intracranial hypertension. | |
| Subarachnoid space | Giant cysts in CSF cisterns | Seizures; focal signs; intracranial hypertension; cognitive impairment. |
| Diffuse arachnoiditis | Focal signs; intracranial hypertension. | |
| Hydrocephalus | Intracranial hypertension; cognitive impairment. | |
| Angiitis | Acute stroke syndromes. | |
| Ventricular system | Ventricular cysts | Focal signs; intracranial hypertension |
| Ependymitis | Seizures; intracranial hypertension | |
| Spinal cord | Arachnoiditis | Root pain; weakness; rarely meningitis |
| Parenchymal cysts | Motor and sensory signs below the level of the lesion | |
| Other | Suprasellar cysticercosis | Ophthalmologic and endocrinologic disturbances |
| Ophthalmic cysticercosis | Visual loss
| |
| Muscle cysticercosis | Muscle pseudohypertrophy |
In areas where neurocysticercosis is common, it is the main cause of adult-onset epilepsy. Seizures are more common in parenchymal neurocysticercosis than in other forms of neurocysticercosis. Seizures may occur at any stage of the disease. Partial seizures are the most common type of seizures. If neurocysticercosis is left untreated seizures will often reoccur, and persist despite treatment. Seizures are more commonly associated with degenerating cysts. These cysts are often accompanied by edema, inflammation, neuronal damage, and gliosis. Seizures are caused by inflammatory responses in the brain and the space-occupying effect of the cysts. Seizures are more common with multiple lesions. Active cysts are associated with first time seizures while calcified granulomas are associated with chronic epilepsy.
Those with neurocysticercosis can exhibit a variety of specific neurologic symptoms determined by the size, number, and location of the parasites. Pyramidal tract symptoms, such as weakness, Babinski's sign, spasticity, and hyperreflexia are the most common; however sensory impairments, parkinsonian rigidity, involuntary movements, language disturbances, and signs of brain-stem dysfunction can also occur. Focal neurologic symptoms are most commonly seen in those with large subarachnoid cysts compressing the brain parenchyma. Those with neurocysticercosis and inflammation of the arachnoid may present with focal signs and ischaemic strokes caused by intracranial artery blockage, cranial nerve compression, hearing loss, facial nerve palsy or trigeminal neuralgia, and focal neurological symptoms caused by brainstem damage. Cysticercosis of the spinal cord often causes radicular pain, weakness, and sensory impairments due to localized mass effects or inflammation in the subarachnoid space.
Intracranial hypertension is associated with neurocysticercosis and may be accompanied by other symptoms. It is more common in extraparenchymal neurocysticercosis. The most common cause of intracranial hypertension in neurocysticercosis is hydrocephalus. Hydrocephalus can be related to granular ependymitis, compression of the CSF pathways by cysts, cysticercotic arachnoiditis, and inflammation or cysts blocking ventricles. Large subarachnoid cysts and cyst clumps can also cause a mass effect and intracranial hypertension, with or without hydrocephalus. Intracranial hypertension can present as episodic loss of consciousness when moving the head, known as Bruns syndrome. Intracranial hypertension may be subacute or chronic. Intracranial hypertension can also be caused by cysticercotic encephalitis, which is a severe type of neurocysticercosis usually affecting younger women and children. Cysticercotic encephalitis is characterized by seizures, intracranial hypertension, clouding of consciousness, papilledema, headache, reduction of visual acuity, and vomiting.
Cognitive and psychiatric manifestations of neurocysticercosis can range from mild deficits to severe dementia. Episodes of psychosis which involve paranoia, confusion, and violent behaviour have been reported to occur with neurocysticercosis. Some of these episodes could be associated with psychomotor epilepsy or postictal psychosis. Other psychiatric symptoms of neurocysticercosis include anxiety, delirium, sensory changes, depression, and personality disorders. Those with neurocysticercosis may exhibit depression, cognitive impairments, or a decline in quality of life.
Spinal arachnoiditis can cause subacute root pain and weakness. Cysts in the spinal cord parenchyma are typically associated with motor and sensory impairments that vary depending on the location of the lesion. Those with cysticerci in the sellar region may have ophthalmologic and endocrinologic symptoms. Intraocular cysticerci are most commonly found in the subretinal space and cause a gradual reduction in visual acuity or visual field abnormalities. The cysts can cause inflammation of the vitreous membrane, uveitis, and endophthalmitis, which is the most serious complication of ocular cysticercosis and can result in phthisis bulbi. Cysticercal infection in striated muscles can cause weakening and hypertrophy over time.
Neurocysticercosis is caused by the larvae of the tapeworm Taenia solium. Neurocysticercosis often results from improperly cooked infected pork or other food, or contaminated water. Once someone consumes Taenia solium, cysticerci are released into the small intestine. The head of the tapeworm (scolex) then evaginates and attaches to the intestinal wall. When the scolex attaches, it grows into a tapeworm which penetrates the intestinal wall and gets into the bloodstream where it can travel the rest of the body.
Taenia solium is a part of the Cestoda class and is a species of the genus Taenia. T. solium has two hosts, pigs and humans. Both can act as an intermediate hosts for the larval form, though humans are the only definitive hosts for the adult cestode. T. solium larvae are cystic, fluid-filled membrane vesicles containing a tapeworm head (scolex) with four suckers and a double crown of hooks, a narrow neck, and a huge body composed of several hundred proglottids. Normally, a human host ingests cysts in infected pork, after which the scolex evaginates and clings to the intestinal wall with its suckers and hooks. Once the scolex is attatched, the proglottids begin to multiply and mature into a 2–4 m ribbon-like tapeworm about 4 months after infection.
When humans consume T. solium eggs, the eggs hatch into larvae that pierce the intestinal mucosa and spread throughout the body, causing cysticercosis. Although cysts can lodge in any tissue, the majority of adult cysts are located in the central nervous system, skeletal muscle, skin, and eyes. Cysticerci penetrate the central nervous system as vesicular (viable) parasites with a transparent membrane, clear vesicular fluid, and a usual invaginated scolex. Cysticerci can live for years or, as a result of the host's immune response, degenerate and convert into inactive nodules. The colloidal stage of cysticerci involution is characterized by murky vesicular fluid and hyaline degeneration of the scolex. The cyst wall next thickens and the scolex transforms into mineralized granules; this phase, in which the cysticercus is no further viable, is known as the granular stage. Finally, the parasite remnants become mineralized nodules (calcified stage).
Neurocysticercosis is often hard to diagnose since the methods used to diagnose it can be unreliable and often hard to access in areas with fewer resources. Physical examination and laboratory testing are often not helpful in diagnosing neurocysticercosis. The diagnosis relies on neuroimaging and serology. Diagnostic criteria have also been created to help with the diagnostic process.
The lentil lectin purified glycoprotein (LLGP) enzyme-linked immunoelectrotransfer blot (EITB) assay, uses specific proteins to detect T. solium antibodies in blood, has given the most reliable results. Antibodies can be identified in EITB as early as 5 weeks after infection. The LLGP-EITB has a sensitivity of 98% for individuals with multiple brain cysts and a specificity of 100%. However, its sensitivity is lower in cases with just one cyst. ELISA detection of anticysticercal antibodies in CSF is 89% sensitive and 93% specific for people with active neurocysticercosis infections and is used when EITB is not available.As many as 37% of those with neurocysticercosis have high eosinophils, making it the most common blood abnormality in neurocysticercosis. The number of people with positive stool tests for Taenia solium eggs in neurocysticercosis varies and seems to depend on how severe the infection is. Recognizing Taenia eggs is difficult, and many cases may go undetected during testing.
CT and MRI give objective information about number and pattern of lesions, the stage of healing, and how the immune system is responding to the parasites. The ability to evaluate views in various spatial planes and the image definition offered by MRI addresses problems relating to seeing bone structures on CT scans, making MRI easier to detect small lesions at the back of the brain or near the skull. CT is more sensitive at detecting calcium buildup in the brain due to its ability detect calcifications in the brain.
Live vesicular cysts are small, round lesions with little swelling around them and do not need contrast for imaging. The tapeworm head (scolex) usually appears as an asymmetric nodule inside the cysts. Multiple live cysts with these heads corroborate the diagnosis. Once the cysts begin to break down (colloid cysts), their borders become unclear, they are surrounded by swelling, and exhibit significant ring or nodular contrast enhancement. Calcified cysticerci are shown on CT scans as non-enhancing hyperdense nodules without swelling.
Neurocysticercosis diagnostic criteria:
Neurocysticercosis can be classified into two main types: parenchymal, which affects the brain tissue, and extraparenchymal, which occurs outside the brain tissue.
Neurocysticercosis is preventable. Some factors that make T. solium potentially eradicable are humans being the only definitive host, the intermediate host being an animal whose exposure to ova can be controlled, well-developed diagnostic testing allowing infected individuals to be identified, effective treatments available, and the availability of pig vaccines.
Neurocysticercosis is more prevalent in areas where the transmission of T. solium is more likely, such as areas with improper disposal of waste, lower levels of education, improper slaughter of pigs, and free-roaming pigs. Unsanitary conditions and domestic pigs are required for T. solium to be transmitted. Urbanization and development cause these factors to go away and therefore transmission goes down as well. Because neurocysticercosis takes years to develop, intervention programs can take decades.
To prevent neurocysticercosis, interventions such as increasing education, improving sanitary conditions, and strict animal husbandry and meat inspection procedures are needed. Medical prevention includes de-worming people with medications such as niclosamide or praziquantel, and vaccinating and treating pigs with oxfendazole. Raised awareness of neurocysticercosis in non-endemic countries where rates are increasing is also important. The TSOL18 vaccine, which is made up of a recombinant protein from a T. solium oncosphere is a promising solution for the prevention and control of neurocysticercosis. Increasing public health surveillance, such as obligatory notification of neurocysticercosis cases, could also be beneficial. Properly identifying neurocysticercosis is needed to target interventions.
In 1985 in Ecuador praziquantel was used for de-worming, and was eventually used in other countries. In Honduras, transmission and morbidity decreased after the health education and control program. A big elimination program managed to eliminate transmission in 105 out of 107 villages by using pig vaccines, human and porcine mass chemotherapy, and stool coproantigen case confirmation.
A single treatment method is not appropriate for every person with neurocysticercosis. The disease has to be characterized in terms of cyst viability, the degree of the host's immunological response to the parasite, and the location and number of lesions to provide proper treatment. Symptomatic and antiparasitic medications are typically used in conjunction for treatment. Surgery can also be used to remove cysts.Neurocysticercosis is a persistent infection, with symptoms appearing months or years later. As a result, removing the parasite is not an emergency, and the first step in treating those with neurocysticercosis is often aimed at minimizing the symptoms. This may be done with the use of antiepileptic, antiedema, analgesic, or anti-inflammatory drugs. Carbamazepine is commonly used to control seizures. Surgery, acetazolamide, steroids, or mannitol may be used to help manage intracranial hypertension.
Antiparasitic drugs are contradicted when there is a preexisting risk of developing hydrocephalus, such as with sub-arachnoid neurocysticercosis or encephalitic neurocysticercosis; in these cases, the inflammation that occurs after treatment may pose a significant risk of rapidly raising intracranial pressure and death. The two most commonly used antiparasitic medications are albendazole, an imidazole that inhibits glucose absorption and metabolism in the parasite, and praziquantel, an isoquinoline which triggers parasite paralysis by altering calcium pathways and homeostasis. These medications are only appropriate for the treatment of vesicular viable cysts or cysts in the early colloidal phases of development, and they are ineffective against calcified cysts.
Steroid administration is an important step in the modulation of neurocysticercosis-related inflammation in the central nervous system, since it controls the acute inflammatory response that occurs following the destruction of live cysts. Prednisolone and dexamethasone are frequently used as adjuncts to antiparasitic therapy.
Antiparasitic medication may be ineffective in cases of severe infection due to the hazards associated with mass inflammation, but these forms of neurocysticercosis carry a high risk of consequences if left untreated. In some circumstances, a more aggressive treatment plan, including surgery, may be required. Surgical treatments include ventricle-peritoneal shunts and excision of cysts.
The prognosis for neurocysticercosis depends on the number and location of the cysts. Single enhancing lesion neurocysticercosis typically has a good prognosis, with lesions resolving within 6 months in over 60% of cases. Multiple or calcified lesions increase the risk of seizure relapses. Although psychiatric and cognitive changes are common with neurocysticercosis, they are usually not severe enough to affect day-to-day behaviour.
Parenchymal neurocysticercosis also has a good prognosis. Parenchymal neurocysticercosis prognosis is mediated by the number of lesions and the severity of the inflammation. Over half of those with calcified parenchymal neurocysticercosis have relapses in seizures and need antiseizure medications long-term.
Extraparenchymal neurocysticercosis does not respond to antiparasitic treatment as well as parenchymal neurocysticercosis, meaning that multiple types or courses of treatment are sometimes needed. Complications from treatment such as shunt blockage or vasculitis are also more prevalent with extraparenchymal neurocysticercosis. Extraparenchymal neurocysticercosis can lead to obstructive hydrocephalus and death.
Neurocysticercosis is endemic in most developing countries, except predominantly Muslim countries. It is endemic in Latin America, China, Nepal, Africa, India, and Southeast Asia. It is more common in poorer countries with improper sanitation and a lack of clean water. Taenia solium is considered rare in developed countries and is usually a result of travelling or immigration. Reports of neurocysticercosis are growing from several wealthy nations, including the USA and the UK, as a result of increased globalization and worldwide travel. Most cases of neurocysticercosis in the US have been reported in the southwestern states. Around 90% of neurocysticercosis diagnoses in the US were immigrants from Mexico or South America.
Studies conducted in endemic countries have shown that neurocysticercosis is a common cause of increased rates of epilepsy. In endemic regions, CNS infection is extremely common; in many of these groups, the frequency of certain serum antibodies is more than 10%, and residual intraparenchymal brain calcifications on CT scans are seen in 10–20% of the general population. Neurocysticercosis is estimated to affect 29% of those with epilepsy. About 15% of the pig farming community in India has asymptomatic neurocysticercosis. According to a North Indian study, the prevalence of neurocysticercosis in rural India was 4.5 per 1000. Twenty-five percent of individuals with active epilepsy had antibodies against T. solium, based on another study from North India. In an Indian hospital series, neurocysticercosis was responsible for more than half of the instances of children with partial seizures.
Descriptions of Taenia solium tapeworms date back to 1500 BC. Taenia solium cysticerci have even been found in ancient Egyptian mummies. The first recorded cases of neurocysticercosis were most likely described by German physician John Wolfgang Rumler in 1558. Hipólito Unanue, a Peruvian physician and journalist, is believed to have first recorded simultaneous taeniasis and cysticercosis in the same individual in 1792: he reported a case involving a soldier with taeniasis who died following a violent seizure. During the 19th century, German pathologists noticed the morphological parallels between the adult T. solium head and the cysticercus scolex. Friedrich Küchenmeister showed that the consumption of cysticercus from pork caused human intestinal taeniasis by feeding a prisoner food that included cysticerci gathered from a recently killed pig. In the second part of the 19th century, research showed that feeding Taenia eggs from infected humans to pigs caused cysticercosis.
Neurocysticercosis was featured in the "Pilot" episode of House M.D. The episode followed a young woman who contracted neurocysticercosis after eating contaminated ham.
Sebastián Ferrat, a Mexican television star, died in 2019 at age 41 from neurocysticercosis. The New York Times stated that RFK Jr. had contracted neurocysticercosis after travelling to Africa, South America, and Asia. Gaius Julius Caesar is believed to have had epilepsy related to cysticercosis.