Annals of B-Pod: Neurocysticercosis
/HISTORY OF PRESENT ILLNESS
The patient is a Hispanic male in his late 20s who is brought in to the emergency department (ED) by family members with a chief complaint of headache, abnormal behavior, and confused speech. He reports gradual onset of a headache two days ago with pain located on the left side of his head and radiating to the front. He denies vision changes, neck pain, fevers, nausea, vomiting, or prior history of headaches. Later in the ED course, the patient provides a different story, complaining of generalized body aches for one hour and stating that he is seeking a primary care doctor for a checkup .
Collateral information obtained from family members reveals that the patient has been exhibiting strange behaviors at home. He has reportedly been more lethargic than usual, having memory issues as evidenced by mixing up past and present events, and talking “out of his head.” They also report a history of fevers, night sweats, and chills for the past two days. Additionally, the patient provides incorrect information regarding how he got to the hospital and who brought him in, and when confronted about this misinformation, seems to be confabulating.
Past Medical History: None
Past Surgical History: None
Medications: None
Allergies: No known allergies
Social History: Originally from Mexico, has lived in the USA for several years. No international travel during this time frame. Works construction. Smokes cigarettes, denies alcohol or drug use.
PHYSICAL EXAM
Vitals: T 36 HR 76 BP 128/73 RR 16 SpO2 98% on RA
The patient is non-toxic appearing and in no acute distress. He is drowsy but arouses to voice and is able to converse and follow commands. He is oriented to self and location, but not to date or time. Pupils are equal and reactive to light, extraocular movements are intact, and there is no evidence of nystagmus. His cranial nerves are intact. Strength, sensation and reflexes in bilateral upper and lower extremities are normal. He has no clonus, ataxia or tremors. No meningismus is noted. The remainder of his exam, including HEENT, cardiac, pulmonary, abdomen and skin, is unremarkable.
DIAGNOSTICS
WBC: 9 Hgb: 16 Hct: 47 Plt: 380
Na: 142 K: 3.7 Cl: 106 HCO3: 27 BUN: 16 Cr: 0.91 Glucose: 100
AST: 17 ALT: 15
Urinalysis: 40 ketones, trace protein
EtOH: <10 UDS: + THC
Influenza: Negative
CT Head: Multiple punctate foci of calcification with moderate ventriculomegaly. Findings concerning for neurocysticercosis with hydrocephalus.
HOSPITAL COURSE
The patient had findings concerning for neurocysticercosis with hydrocephalus on non-contrast head CT. Neurology and neurosurgery were consulted, and an MRI brain with and without contrast was obtained. The MRI demonstrated a cystic mass in the third ventricle with an enhancing central nodule, consistent with intraventricular neurocysticercosis resulting in obstructive hydrocephalus. Lumbar puncture was deferred given the obstructive hydrocephalus, and the patient was admitted to the neurology service on a step-down status for further management. Ophthalmology performed a dilated eye exam that ruled out any signs of ocular involvement.
While inpatient, infectious disease was consulted. The patient was started on dexamethasone 0.1 mg/kg/day immediately, and began albendazole 15 mg/kg/day and praziquantal 50 mg/kg/day on hospital day two. Additional infectious work up, including HIV, strongyloides, and quantiferon TB tests were negative. Cysticercosis serum testing was positive. Several days later, neurosurgery performed endoscopic resection of the cyst in the third ventricle and placed an external ventricular drain. The patient tolerated the procedure well and his post-operative CT scan demonstrated immediate improvement in his hydrocephalus. The external ventricular drain was removed and the patient was to continue anti-helminths for a total of ten days and remain on steroids during this course. His neurologic exam improved throughout the hospital course, and he was discharged one week into this hospitalization. He followed up with neurosurgery at two and six weeks postoperatively and was noted to be recovering well with only intermittent headaches.
neurocysticercosis
Epidemiology and Pathophysiology
Cysticercosis is an infection caused by the larval stage of the tapeworm Taenia solium, commonly referred to as the “pork tapeworm.” Among its infectious manifestations is neurocysticercosis, which is the most common parasitic infection of the central nervous system and one of the most common causes of epilepsy worldwide. [1] Neurocysticercosis is endemic to Latin America, Africa, South East Asia, India, China and Nepal. [1] It is not endemic to the United States, and cases are mainly due to immigration or travel from endemic countries rather than local transmission.
Humans become infected with neurocysticercosis after ingestion of T. solium eggs that have been shed in the stool of a human tapeworm carrier, typically via contaminated food or water. Following ingestion, embryos hatch in the small intestine, invade the bowel wall, enter the blood stream and then spread throughout the body, including the brain, muscle, and liver. The parasite then forms cysts in the tissue over a period of three to six weeks; those located in the brain and central nervous system cause neurocysticercosis. Of note, it is a common misconception that neurocysticercosis infection is caused by eating under-cooked pork infected with T. solium. Individuals who ingest under-cooked infected pork can acquire an intestinal tapeworm infection, but only individuals who ingest the eggs in the stool of human carriers develop neurocysticercosis. [2,3]
Clinical Presentation
Clinical manifestations and severity of neurocysticercosis vary widely based on characteristics of the infection and host (number, size, location of cysts and intensity of host’s immune response). The symptomatology of neurocysticercosis can be separated into two main groups, intraparenchymal or extraparenchymal.
Intraparenchymal lesions are more common, with onset usually occurring a few years from initial infection. [4] Location and degenerating stage of cysts affect the timing and symptomology demonstrated, with newer developing cysts instigating an intense inflammatory response, and older calcified cysts that may be asymptomatic with only intermittent flares of inflammation. [4] In general, intraparenchymal cysts are most commonly associated with focal seizures with secondary generalization and headache, less commonly with altered vision and focal neurologic deficits, and rarely, psychiatric symptoms. [2,3] If a large number of parenchymal cysts are present, leading to a significant host inflammatory response, the patient may present with a clinical picture resembling encephalitis. Because the onset of symptoms can be subacute and subclinical, many cases are identified incidentally when neuroimaging is performed for other reasons in patients who are asymptomatic or who have less severe presentations of the disease. [5]
In contrast, extraparenchymal cysts, particularly cysts located in the intraventricular and subarachnoid spaces, are associated with symptoms of elevated intracranial pressure, such as headache, nausea, vomiting, and visual disturbances due to a massive inflammatory response or direct obstruction of cerebrospinal fluid flow, and may be accompanied by altered mental status. Mobile lesions in the third or fourth ventricle can cause intermittent obstruction depending upon patient positioning, leading to episodic symptoms. Spinal cord lesions are exceedingly rare, and can cause radicular pain and sensimotor deficits. [2,3] Lastly, ocular lesions can involve any portion of the globe and cause impaired vision, diplopia, and blindness. Ophthalmologic examination to rule out ocular involvement is paramount prior to initiation of anti-parasitic therapy as treatment can otherwise cause ocular inflammation and blindness if parasites are not surgically removed from the eye prior to systemic therapy. [6] Direct visualization of the parasite can be done via fundoscopic exam.
Diagnosis
Diagnosis of neurocysticercosis starts with a travel history, since patients who have not been to an endemic country are unlikely to have the disease. However, suspicion must remain high in patients who have ever traveled to endemic areas, even for brief periods of time, as disease course can be indolent and develop several years after initial infection. CT or MRI of the head confirm the diagnosis. Radiographic findings can vary, including cystic lesions, enhancing lesions and calcifications, and findings can demonstrate cysts in different stages. Pathognomonic findings include identification of the scolex of the tapeworm within the cystic lesion. CT is more sensitive for identifying calcifications and ocular involvement, whereas MRI can help detect smaller lesions and evaluate for degenerative change and edema.[3,6] Serologic testing should be performed as confirmation, especially when CT/MRI are suggestive but not diagnostic. The serologic test of choice is enzyme-linked immunoelectrotransfer blot (EITB) using parasite glycoproteins performed on serum. [6,7] Sensitivity for serum testing is generally greater than cerebrospinal fluid testing, but is directly related to the number of lesions, and thus can be unreliable in single lesion cases.
If clinical suspicion remains high despite equivocal findings using the diagnostic testing above, brain biopsy can be performed to confirm a diagnosis.
Treatment and Prognosis
Treatment of neurocysticercosis is focused both on treating the underlying infection as well as the complications of the disease process. [6] The order of the treatment employed largely depends on the severity of the clinical presentation. If a patient presents in status epilepticus or with severely increased intracranial pressure, measures for treating these life-threatening conditions outweigh initiation of antiparasitics. Thus, evaluation of airway protection along with quick initiation of anti-epileptics or emergent external ventricular drain placement take precedence, if needed. Furthermore, initiation of antiparasitic therapy can risk exacerbating severe neurologic symptoms due to increasing inflammatory response around the degenerating cysts, especially in patients with a large disease burden.
In treating less emergent complications, such as seizures and cerebral edema, first-line antiepileptic drugs (AED) are as effective in neurocysticercosis as in treating idiopathic epilepsy, and patients should remain on AED therapy for at least two years afterward to prevent recurrent seizures. [2] As discussed before, a significant inflammatory response can be seen in neurocysticercosis, and subsequently corticosteroids are universally used. A trial of dexamethasone 0.2-0.4 mg/kg per day should be initiated. Therapy can hasten resolution of active cysts, diminish seizure risk, and reduce likelihood of recurrent hydrocephalus. Duration of steroids may differ depending upon disease burden and location, but will usually accompany at least the duration of anti-parasitic treatment. Prior to initiation of long-term steroids, serum testing for latent tuberculosis and strongyloides should be completed.
In terms of antiparasitic treatment, both albendazole and praziquantel are cysticidal, resulting in eventual cyst resolution and calcification. However, use of these agents should be in conjunction with an infectious disease specialist, as location and number of cysts can affect the efficacy of each drug. Antiparasitic treatment is usually delayed until steroids have been administered in order to prevent worsening inflammatory response. Furthermore, a patient can have cysts in several different stages at the time of treatment, requiring a prolonged course until all cysts have resolved. Monotherapy can be used in patients with one to two cysts, with a typical regimen being albendazole 15 mg/kg per day divided in two doses. For patients with greater than two cysts, treatment is most effective with albendazole in addition to praziquantel 50 mg/kg per day divided in three doses. [2] Treatment duration is, at minimum, ten days. Follow up neuroimaging is usually conducted biannually until resolution of cysts are evident. [4] If cystic lesions persist, additional therapy is warranted.
Neurosurgical intervention, including neuroendoscopy, cyst removal, and shunt placement, may offer the benefit of removing source of infection and reducing the length of antiparasitic and corticosteroid courses required. Obstructive hydrocephalus requires surgical intervention, as seen in our case, while communicating hydrocephalus may ultimately require a ventriculoperitoneal shunt. [6]
In terms of prognostication, intraparenchymal cysts tend to respond better to the above therapies when compared to extraparenchymal cysts, with single cysts portending a better outcome than numerous cysts. Extraparenchymal neurocysticercosis has a worse prognosis, thought to be secondary to larger parasite loads and less restricted growth of individual cysts. [3]
SUMMARY
In summary, although neurocysticercosis is not endemic to the United States, clinical suspicion for this disease process must remain high in patients with any travel history to endemic regions, especially immigrants, as the disease process can be chronic and subclinical, and with high morbidity and mortality. Emergent diagnosis and immediate treatment for complications is paramount, and these patients should be co-managed with infectious disease, neurology, and neurosurgery, as long-term treatment and follow up is needed.
References
Fabiani S, Bruschi F. Neurocysticercosis in Europe: still a public health concern not only for imported cases. Acta tropica. 2013 Oct 1;128(1):18-26.
Garcia HH, Nash TE, Del Brutto OH. Clinical symptoms, diagnosis, and treatment of neurocysticercosis. The Lancet Neurology. 2014 Dec 1;13(12):1202-15.
Gripper LB, Welburn SC. Neurocysticercosis infection and disease–A review. Acta tropica. 2017 Feb 1;166:218-24.
Nash TE, Garcia HH. Diagnosis and treatment of neurocysticercosis. Nat Rev Neurol 2011; 7:584.
Carabin H, Ndimubanzi PC, Budke CM, Nguyen H, Qian Y, Cowan LD, Stoner JA, Rainwater E, Dickey M. Clinical manifestations associated with neurocysticercosis: a systematic review. PLoS neglected tropical diseases. 2011 May 24;5(5):e1152.
White Jr AC, Coyle CM, Rajshekhar V, Singh G, Hauser WA, Mohanty A, Garcia HH, Nash TE. Diagnosis and treatment of neurocysticercosis: 2017 clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clinical Infectious Diseases. 2018 Feb 22;66(8):e49-75.
Tsang VC, Brand JA, Boyer AE. An enzyme-linked immunoelectrotransfer blot assay and glycoprotein antigens for diagnosing human cysticercosis (Taenia solium). Journal of Infectious Diseases. 1989 Jan 1;159(1):50-9.
