A Previously Healthy 27-Year-Old Man With New-Onset Seizure

Correct answer: B. Neurocysticercosis

The patient's condition was diagnosed as neurocysticercosis (NCC) based on new-onset seizure, history of travel to an endemic area, and consistent findings on neuroimaging. Pertinent negative screening tests lowered suspicion for other etiologies. NCC is the parasitic infestation of Taenia solium larvae in the central nervous system (CNS) and may commonly present as new-onset seizures in adults who live in both developing and developed countries.

Differential diagnosis. Like NCC, glioblastoma multiforme (GBM) and other high-grade gliomas can present as a ring-enhancing lesion with surrounding edema. However, they are notoriously aggressive and progress rapidly and may be rather sizable at an average of 4 cm diameter at the time of diagnosis, with irregular margins and a necrotic or hemorrhagic center.^1,2 Regarding the patient case, the lesion was much smaller than a typical GBM at diagnosis, the borders were more uniform and well-defined, and there was no evidence of central necrosis. However, to definitively rule out malignancy, tissue sampling may be required.³

Cerebral pyogenic abscesses commonly occur after bacterial infections and appear as pus surrounded by a vascularized capsule, with ring-enhancement occurring later in the disease process. Seizures can be an early presenting symptom, although headaches are more common. Patients may also have various symptoms determined by the site of origin.⁴ The patient from the case study was afebrile and had no identifiable source of bacterial infection in the history or on physical examination, thus rendering pyogenic abscess lower on the differential. 

Histoplasmosis of the CNS may present with ring-enhancing lesions in the presence of HIV/AIDS.⁵ This fungal disease typically presents with constitutional symptoms such as fever, fatigue, weight loss, and other organ involvement, such as respiratory symptoms.⁶ The patient did not have HIV or other immunosuppressive illnesses and did not exhibit systemic symptoms.

A tuberculoma is a rare but serious presentation of tuberculosis involving the brain. While both NCC and tuberculomas have similar presenting symptoms and increased prevalence in underdeveloped countries, radiographically tuberculomas are typically larger than 20 mm, solid-appearing, and irregularly shaped.⁵ However, it is reasonable to screen such patients for tuberculosis.⁷ The patient in this case had a negative tuberculosis screening which was reassuring and thus lowered the concern for tuberculoma.

Treatment and management. The patient was managed by a multidisciplinary team, including infectious disease, neurosurgery, and neurology specialists. Antiparasitic medications were not initiated due to nonviable disease. Dexamethasone and levetiracetam were initiated for symptomatic management while inpatient. Dexamethasone was discontinued upon being discharged from the hospital. The patient experienced severe nausea with oral levetiracetam 500 mg twice daily and was switched to oral clonazepam 0.5 mg twice daily for seizure prophylaxis. The lesion remained stable on a 1-month follow-up brain MRI. Four months after initial hospitalization, the patient and neurosurgeon ultimately opted for biopsy and surgical resection to prevent seizure recurrence and for definitive diagnosis. The patient tolerated the surgery without complications. Postoperative brain imaging was performed 1 month later, noting resolution of previously abnormal findings. The patient was released from the neurosurgeon and continued care with a neurologist who conducted electroencephalography with provocation induction and further neuroimaging over the following 6 months. The clonazepam was decreased to 0.25 mg twice daily and then discontinued 8 months after surgery

Outcome and follow-up. Nine years later, the patient remains seizure-free without complications.  

Discussion. T solium, colloquially named the pork tapeworm, is endemic to regions of Latin America, Asia, sub-Saharan Africa, and Oceania; it is the most common cause of acquired epilepsy in the world.⁸ While T solium is more prevalent in developing countries, especially in areas with freely roaming livestock and poor sewage conditions, NCC can affect nonendemic populations as well as people who do not consume pork.⁹

Two distinct conditions can arise from infection of T solium: cysticercosis and taeniasis. Cysticercosis is transmitted fecal-orally when T solium eggs are ingested by a human or pig host. Oncospheres hatch out of the host’s small intestines, invade the bloodstream, and in their larval stage, form cysts called cysticerci in surrounding muscle, tissue, and organs. When cysticerci develop in the CNS, the infection is called NCC.¹⁰

Taeniasis occurs when humans ingest T solium in the form of cysticerci from contaminated, undercooked pork.¹¹ The scolex, which is the anterior segment of the larvae containing suckers and hooks, evaginates from the cysticerci, attaches to the host’s intestines, and develops into the adult stage of the tapeworm. Patients with taeniasis are generally asymptomatic. The tapeworm continues its life cycle contained within the small intestines, excreting eggs in the stool of infected hosts, which in turn causes cysticercosis if ingested by pigs or humans.¹¹ 

NCC generally progresses through three stages. The vesicular stage consists of viable cyst(s), which can go unnoticed for years by the host’s immune system.¹² The colloidal/degenerating stage involves the gradual breakdown of cysts by the host’s inflammatory cells.^12,13 The final calcific or nonviable stage occurs when cyst remnants become fibrotic and calcified, and may be associated with surrounding edema, inflammation, and gliosis.¹² Seizures most commonly develop in the nonviable stage, and are therefore widely attributed to pericystic scarring, mass effect, and immune-mediated response to the dead parasite.¹³ However, seizures have been noted during the viable stage or in the absence of edema, thus entertaining the possibility for other pathogenic processes contributing to seizures.^12,13

Proposed mechanisms include proinflammatory cytokines causing serum albumin to leak through the blood-brain barrier, resulting in epileptiform activity; genetically predisposed low seizure thresholds due to polymorphisms of host Toll-like receptor 4; and increased release of seizure-provoking neurotransmitters, such as substance P and glutamate due to neuronal damage.¹² Because NCC mainly affects underdeveloped countries with limited resources, most of these theories are derived from clinical correlation rather than experimental studies.¹² 

Patients with NCC can present with seizures, headaches, or other neurologic deficits related to increased intracranial pressure, such as nausea, vomiting, or altered mental status.¹⁴ NCC can be further classified as parenchymal, which are more common and present mainly as seizures, or extraparenchymal, which are more rare but serious, especially when affecting the eye, spinal cord, subarachnoid, or ventricles.¹⁵ 

Patients may remain asymptomatic for 3 to 5 years, with some reports of symptom onset occurring after 30 years.¹⁶ There are no clear indicators to predict symptom progression or disease potential for patients with NCC. Assessing the ratio of asymptomatic to symptomatic patients in endemic areas also poses a challenge because those without symptoms are not likely to receive diagnostic testing. However, in a notable 2007 study conducted among a North Indian pig farming community, researchers evaluated asymptomatic family members of patients with symptomatic NCC; they found that 29% of asymptomatic people tested positive for NCC.¹³ These patients were followed for 6 months, during which time they remained symptom-free.¹³    

The diagnosis of symptomatic NCC can be made based on clinical and epidemiologic suspicion, and neuroimaging with either MRI or CT.⁷ NCC can present on imaging as cystic or calcified lesions, with or without presence of scolex, measuring up to 20 mm.⁵ As the cyst degenerates, it may appear as a ring-shaped enhancement with surrounding edema on MRI with contrast.¹⁷ CT is generally considered more sensitive for detecting calcifications, while MRI typically allows for better overall detection of all stages of NCC.¹³ Serum antigen assays can be used to confirm NCC if neuroimaging is unclear, with enzyme-linked immunoelectrotransfer blot having the highest sensitivity and specificity of these tests (98% and 100%, respectively).¹³ Screening household members for taeniasis can be considered, especially in nonendemic areas.⁷

Prevention of cysticercosis hinges on disrupting the fecal-oral transmission cycle of the parasite with proper community sanitation solutions, good hand hygiene, thoroughly washing food, and eradicating tapeworms from human carriers with antiparasitic medications.¹¹ Preventing taeniasis can also prove beneficial in cysticercosis prevention, which focuses mainly on properly inspecting, preparing, and cooking meat. Porcine vaccinations are also highly effective and used in endemic regions.¹¹

Treatment of NCC largely depends on the stage of NCC at diagnosis and associated symptoms. Antiparasitics are beneficial in treating viable cysts. The recommended treatment is albendazole (15 mg/kg daily over two doses) for 2 weeks, with the addition of praziquantel (50 mg/kg daily over three doses) if needed for multiple lesions.¹⁸ Neuroimaging is recommended every 6 months until the lesion has resolved.⁷

Antiparasitics may worsen neurologic symptoms during the degradation process, and therefore should be coadministered with corticosteroids, such as dexamethasone (0.1 mg/kg per day), which can help reduce inflammation and brain edema.¹⁴ Antiepileptic medication can be used symptomatically, and may be continued for 6 months in patients with single cysts or up to 24 months with multiple lesions or recurrent seizures.⁷ Shunt placement or surgical removal of the cyst is required in those with increased intracranial pressure.⁵ 

References

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AFFILIATIONS:
¹Department of Family Medicine, Philadelphia College of Osteopathic Medicine Georgia, Suwanee, GA
²Philadelphia College of Osteopathic Medicine Georgia, Suwanee, GA

CITATION:
Zarandy J, Thompson V, Ho A, Doyle C. A previously healthy 27-year-old man with new-onset seizure. Consultant. 2023;63(11):e2. doi:10.25270/con.2023.09.000004

Received March 27, 2023. Accepted June 6, 2023. Published online September 14, 2023.

DISCLOSURES:
The authors report no relevant financial relationships.

ACKNOWLEDGEMENTS:
None.

CORRESPONDENCE:
Joy Zarandy, DO, Assistant Professor of Family Medicine, Philadelphia College of Osteopathic Medicine – Georgia Campus, 625 Old Peachtree Road NW, Suwanee, GA 30024 (joyza@pcom.edu)

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