The returned traveler with neurologic manifestations: could my patient have a parasite?

PURPOSE OF REVIEW: The present review focuses on parasitic infections of the central nervous system (CNS) that can affect the international traveler. RECENT FINDINGS: The epidemiology of imported parasitic infections is changing and clinicians are treating increasing numbers of returned travelers with parasitic infections in the CNS with which they are not familiar. SUMMARY: The epidemiology, life cycle, clinical manifestations, diagnosis, and treatment of parasites that affect the CNS will be discussed.

Cerebrospinal Fluid Analysis.

Cerebrospinal fluid (CSF) analysis is a diagnostic tool for many conditions affecting the central nervous system. Urgent indications for lumbar puncture include suspected central nervous system infection or subarachnoid hemorrhage. CSF analysis is not necessarily diagnostic but can be useful in the evaluation of other neurologic conditions, such as spontaneous intracranial hypotension, idiopathic intracranial hypertension, multiple sclerosis, Guillain-Barré syndrome, and malignancy. Bacterial meningitis has a high mortality rate and characteristic effects on CSF white blood cell counts, CSF protein levels, and the CSF:serum glucose ratio. CSF culture can identify causative organisms and antibiotic sensitivities. Viral meningitis can present similarly to bacterial meningitis but usually has a low mortality rate. Adjunctive tests such as CSF lactate measurement, latex agglutination, and polymerase chain reaction testing can help differentiate between bacterial and viral causes of meningitis. Immunocompromised patients may have meningitis caused by tuberculosis, neurosyphilis, or fungal or parasitic infections. Subarachnoid hemorrhage has a high mortality rate, and rapid diagnosis is key to improve outcomes. Computed tomography of the head is nearly 100% sensitive for subarachnoid hemorrhage in the first six hours after symptom onset, but CSF analysis may be required if there is a delay in presentation or if imaging findings are equivocal. Xanthochromia and an elevated red blood cell count are characteristic CSF findings in patients with subarachnoid hemorrhage. Leptomeningeal carcinomatosis can mimic central nervous system infection. It has a poor prognosis, and large-volume CSF cytology is diagnostic.

Central Nervous System Infections in the Immunocompromised Adult Presenting to the Emergency Department.

Over the past 2 decades, the population of immunocompromised patients has increased dramatically in the United States. These patients are at elevated risk for both community-acquired and opportunistic central nervous system infections. We review the most common and serious central nervous system pathogens affecting these patients and outline a diagnostic and therapeutic approach to their management in the emergency department. We recommend a broad diagnostic evaluation, including neuroimaging and cerebrospinal fluid studies where appropriate, empiric antimicrobial therapy, and early involvement of subspecialists to provide comprehensive care for these complex patients.

Case report: multiple and atypical amoebic cerebral abscesses resistant to treatment.

BACKGROUND: The parasite Entamoeba histolytica is the causal agent of amoebiasis, a worldwide emerging disease. Amebic brain abscess is a form of invasive amebiasis that is both rare and frequently lethal. This condition always begins with the infection of the colon by E. histolytica trophozoites, which subsequently travel through the bloodstream to extraintestinal tissues. CASE PRESENTATION: We report a case of a 71-year-old female who reported an altered state of consciousness, disorientation, sleepiness and memory loss. She had no history of hepatic or intestinal amoebiasis. A preliminary diagnosis of colloidal vesicular phase neurocysticercosis was made based on nuclear magnetic resonance imaging (NMRI). A postsurgery immunofluorescence study was positive for the 140 kDa fibronectin receptor of E. histolytica, although a serum analysis by ELISA was negative for IgG antibodies against this parasite. A specific E. histolytica 128 bp rRNA gene was identified by PCR in biopsy tissue. The final diagnosis was cerebral amoebiasis. The patient underwent neurosurgery to eliminate amoebic abscesses and was then given a regimen of metronidazole, ceftriaxone and dexamethasone for 4 weeks after the neurosurgery. However, a rapid decline in her condition led to death. CONCLUSIONS: The present case of an individual with a rare form of cerebral amoebiasis highlights the importance of performing immunofluorescence, NMRI and PCR if a patient has brain abscess and a poorly defined diagnosis. Moreover, the administration of corticosteroids to such patients can often lead to a rapid decline in their condition.

Toxocara Brain Infection in Pigs is Not Associated with Visible Lesions on Brain Magnetic Resonance Imaging.

Human exposure to Toxocara spp. is very frequent, and its larvae can cross the blood-brain barrier and invade the central nervous system (CNS), causing neurotoxocariasis. We aimed to establish a neurotoxocariasis animal model in pigs confirmed by necropsy. Also, the presence of larvae in the CNS was assessed using magnetic resonance imagings (MRIs), to establish brain lesions caused by the larvae migration. Ten pigs were infected intraperitoneally with 3,000 Toxocara larvae. Cerebral toxocariasis was evaluated using MRIs at days 7, 14, 21, and 49, and pigs were euthanized after the examination. Brain tissues were examined by microscopy, and five pigs presented Toxocara, most frequently at day 21 after infection. None of the 10 pigs showed alterations on MRIs. Our study confirms that intraperitoneal Toxocara infection produces neurotoxocariasis in pigs. Toxocara larvae passage through the brain does not seem to produce lesions detectable at MRIs.

Neurotoxocariasis.

Human toxocariasis, caused by larvae of the Toxocara spp., is one of the most prevalent zoonosis with a worldwide distribution. Toxocara larvae can cross the blood-brain barrier, invading the central nervous system (CNS), leading to neurotoxocariasis. The clinical presentation consists of a wide spectrum of neurological manifestations such as meningitis, encephalitis, myelitis and cerebral vasculitis, but asymptomatic CNS infection is common. Despite the high seroprevalence, neurotoxocariasis is thought to be rare, even if in many animal models larvae usually migrate to the brain. Indeed, diagnosis of neurotoxocariasis is rarely considered, and the exact prevalence of CNS involvement is still unknown. Diagnosis of neurotoxocariasis is generally based on the detection of specific antibodies to Toxocara excretory-secretory antigens by ELISA in CSF or serum, and clinical and radiological improvement after anthelmintic therapy, but definitive diagnosis is given by histological confirmation, which is rarely available. Treatment is based on anti-helminthic drugs, commonly albendazole, generally administered with concomitant corticosteroids coverage. At the population level, serological studies suggest an association between Toxocara infections and epilepsy, as well as with other neurodegenerative and psychiatric disorders. Nonetheless the possible role of Toxocara spp. in the pathogenesis of these disorders is still matter of debate.

Molecular and Histologic Diagnosis of Central Nervous System Infections.

Infections of the central nervous system cause significant morbidity and mortality in immunocompetent and immunocompromised individuals. A wide variety of microorganisms can cause infections, including bacteria, mycobacteria, fungi, viruses, and parasites. Although less invasive testing is preferred, surgical biopsy may be necessary to collect diagnostic tissue. Histologic findings, including special stains and immunohistochemistry, can provide a morphologic diagnosis in many cases, which can be further classified by molecular testing. Correlation of molecular, culture, and other laboratory results with histologic findings is essential for an accurate diagnosis, and to minimize false positives from microbial contamination.

Parasitic Infections of the Nervous System.

Parasitic infections of the central nervous system are much more common than suspected, although most infections are asymptomatic. For example, parasites like the ubiquitous protozoa Toxoplasma gondii or the nematode larvae Toxocara canis infect significant proportions of the human population. Other parasitic infections such as malaria and neurocysticercosis are widespread in developing countries and become major causes of neurological morbidity in these regions as well in immigrants and travelers. This article reviews parasitic pathogens causing neurological morbidity and mortality, including an extensive list of less common parasitic infections of the human nervous system.

Baylisascariasis: A young boy with neural larva migrans due to the emerging raccoon round worm.

A 17-month-old boy from Vancouver, Canada, presented with a 5-day history of progressive somnolence, ataxia, and torticollis. Additional investigations revealed eosinophilic encephalitis with deep white matter changes on MR imaging. On day 13, serology came back positive for Baylisascaris procyonis antibodies. While prophylaxis after ingestion of soil or materials potentially contaminated with raccoon feces can prevent baylisascariasis, timely treatment can sometimes alter a disastrous outcome. Populations of infected raccoons are propagating globally, but cases of Baylisascaris neural larva migrans have so far only been reported from North America.

Fungal and Parasitic CNS Infections.

Central nervous system fungal infections can be broadly divided into those that infect a healthy host such as Cryptococcus, Coccidioides, Histoplasma, Blastomyces, Sporothrix spp., and those that cause opportunistic infections in an immunocompromised host such as Candida, Aspergillus, Zygomycetes, Trichosporon spp. The clinical manifestations of central nervous system fungal infections commonly seen in children in clinical practice include a chronic meningitis or meningoencephalitis syndrome, brain abscess, rhino-cerebral syndrome and rarely, a fungal ventriculitis. Fungal central nervous system infections should be suspected in any child with subacute to chronic febrile encephalopathy or meningitis with or without raised intracranial pressure, seizures, orbital pain and/or sero-sanguinous nasal discharge. Diagnosis is corroborated by cerebrospinal fluid analysis, culture and PCR, special stains, serological tests and neuroimaging. Management of fungal central nervous system infections include specific antifungal therapy and supportive measures for associated problems, management of underlying predisposing condition and surgical intervention in cases with localized disease, abscess or presence of simultaneous foreign body such as intracranial shunts. In addition to the fungi, several parasitic infections can cause central nervous system infections in children. Of these, authors briefly discuss cerebral malaria, and amebic meningo-encephalitis.

Cerebral cystic echinococcosis in Mongolian children caused by Echinococcus canadensis.

Recent molecular re-evaluation of Echinococcus granulosus, which causes cystic echinococcosis (CE), has revealed that it is not a single species, but instead consists of 5 cryptic species. Among them, E. granulosus (dog-sheep strain) is predominant (75%) followed by Echinococcus canadensis (22%). The major affected organs, in humans, are the liver (88%) and lungs (11%). Primary cerebral CE comprises less than 1% of all cases. As cerebral CE cases are rare, there are few reports with molecular confirmation of the causative species. This study reports mitochondrial gene analysis from 4 Mongolian pediatric cerebral CE cases. Molecular confirmation was obtained for 3 of the 4 cases, with all 3 cases determined to be due to E. canadensis (G6/G7) infection. None of the cases had other organ involvement. This is only the third report on the molecular identification of the Echinococcus species responsible for cerebral CE, and only the second report of E. canadensis (G6/G7) being the causative agent of cerebral CE.

Takotsubo cardiomyopathy associated with Paragonimiasis westermani.

An 11-year-old boy collapsed during morning assembly at his junior high school. The automated external defibrillator detected ventricular fibrillation and provided shock delivery. He was successfully resuscitated and reverted to sinus rhythm. Electrocardiography showed ST-T elevation in the precordial leads. Echocardiography and angiography demonstrated akinesia of the apex and mid-wall of the left ventricle with preserved contraction of the basal segments, which suggested Takotsubo cardiomyopathy. The patient and his family had often eaten uncooked crab, and his father had a past history of infection with Paragonimiasis westermani. The patient had had a persistent cough and chest pain for several weeks. Chest radiograph showed cystic cavities in the left upper lung. Microbiological examination of the sputum demonstrated an egg of P. westermani and immunological assay showed a raised antibody titre to P. westermani. On the12th day of admission, he developed seizures, and magnetic resonance imaging demonstrated cerebral involvement. After the administration of praziquantel for 3 days, the clinical manifestations improved immediately, and echocardiography normalised within 3 weeks. The patient was discharged on the 32nd day + and follow-up was normal. Takotsubo cardiomyopathy following a potentially fatal arrhythmia is a rare cardiac complication associated with pulmonary and central nervous system infection by P. westermani.

Neuroinvasions caused by parasites

Parasitic diseases of the central nervous system are associated with high mortality and morbidity. Many human parasites, such as Toxoplasma gondii, Entamoeba histolytica, Trypanosoma cruzi, Taenia solium, Echinococcus spp., Toxocara canis, T. cati, Angiostrongylus cantonensis, Trichinella spp., during invasion might involve the CNS. Some parasitic infections of the brain are lethal if left untreated (e.g., cerebral malaria ­ Plasmodium falciparum, primary amoebic meningoencephalitis (PAM) ­ Naegleria fowleri, baylisascariosis ­ Baylisascaris procyonis, African sleeping sickness ­ African trypanosomes). These diseases have diverse vectors or intermediate hosts, modes of transmission and endemic regions or geographic distributions. The neurological, cognitive, and mental health problems caused by above parasites are noted mostly in low-income countries; however, sporadic cases also occur in non-endemic areas because of an increase in international travel and immunosuppression caused by therapy or HIV infection. The presence of parasites in the CNS may cause a variety of nerve symptoms, depending on the location and extent of the injury; the most common subjective symptoms include headache, dizziness, and root pain while objective symptoms are epileptic seizures, increased intracranial pressure, sensory disturbances, meningeal syndrome, cerebellar ataxia, and core syndromes. Many early symptoms of CNS invasion are often nonspecific therefore a diagnosis can be difficult. This article presents the epidemiology, pathophysiology and clinical manifestations of selected parasitic neuroinfections.

Parasitic diseases of the central nervous system: lessons for clinicians and policy makers.

Parasitic diseases of the central nervous system are associated with high mortality and morbidity, especially in resource-limited settings. The burden of these diseases is amplified as survivors are often left with neurologic sequelae affecting mobility, sensory organs, and cognitive functions, as well as seizures/epilepsy. These diseases inflict suffering by causing lifelong disabilities, reducing economic productivity, and causing social stigma. The complexity of parasitic life cycles and geographic specificities, as well as overlapping clinical manifestations in the host reflecting the diverse pathogenesis of parasites, can present diagnostic challenges. We herein provide an overview of these parasitic diseases and summarize clinical aspects, diagnosis, therapeutic strategies and recent milestones, and aspects related to prevention and control.

A rare case of cerebral hydatidosis caused by a G1 genotype of Echinococcus granulosus in a cow from Iran.

Hydatidosis is a medically and veterinary important parasitic disease that is endemic in many parts of the world. Unilocular hydatid cysts may develop in almost any part of the body. Up to 70% of hydatid cysts are located in the liver, followed by 25% in the lungs. Cerebral hydatidosis is an uncommon manifestation of the disease, occurring in less than 1/1000 infected hosts, yet diagnosis does pose a problem. We have reported an exceptionally rare case of cerebral hydatidosis in cattle. This is the first report to describe the characteristic pathological features of the cerebral hydatidosis in cattle caused by the G1 genotype of Echinococcus granulosus. Genotypic analysis was performed on a hydatid cyst from a cow originating from southern Iran, based on the sequence analysis of the cox1 mitochondrial gene.

Cerebral paragonimiasis: a retrospective analysis of 27 cases.

OBJECT: The authors retrospectively analyzed the clinical characteristics, existing problems, and treatment experiences in recently diagnosed cerebral paragonimiasis (CP) cases and sought to raise awareness of CP and to supply reference data for early diagnosis and treatment. METHODS: Twenty-seven patients (22 male and 5 female; median age 20.3 years, range 4-47 years) with CP were diagnosed between September 2008 and September 2013. These diagnoses were confirmed by IgG enzyme-linked immunosorbent assays. Follow-up was performed in 24 cases for a period of 6-56 months. RESULTS: Cerebral paragonimiasis accounted for 21.6% of paragonimiasis cases (27 of 125). The average duration from onset to praziquantel treatment was 69 days. All patients resided in rural areas. Twenty patients had positive lung results, which included visible lung lesions in 14 cases. The lesions were surgically removed in 8 of these cases. Twenty-four patients had high eosinophil counts (≥ 0.08 × 10(9)/L), and eosinophilic meningitis was noted in 17 cases. The rate of misdiagnosis and missed diagnosis was 30.4%. Most symptoms were markedly improved after treatment, but mild movement disorders combined with impaired memory and personality changes remained in a small number of patients. CONCLUSIONS: Clinicians should be alert to the possibility of CP in young patients (4-16 years) with the primary symptoms of epilepsy and hemorrhage. Early diagnosis and timely treatment can reduce the need for surgery and further impairments to brain function. Liquid-based cytological examination of CSF and peripheral blood eosinophil counts can aid in differentiating CP from similar lesions.

Parasitoses with central nervous system involvement.

Most of the parasitoses manifest systemically, including the central nervous system (CNS). Among the most prevalent parasitoses in Central Europe (cysticercosis, toxocarosis, echinococcosis, and toxoplasmosis), cerebral involvement is well recognized and part of the clinical presentation, which cannot be neglected. CNS involvement results from invasion of larvae of these parasites via the blood stream or by direct migration into the CNS. Most frequently larvae reside within the cerebral parenchyma, but sometimes also within the ventricles, in the meningeas within cerebral aneurysms, or in the parenchyma of the spinal cord. Depending on the stage of their development, they cause a local defect or more widespread damage, such as encephalitis, ventriculitis, ependymitis, arachnoiditis, meningitis, myelitis, polyradiculitis, mechanical obstruction of the arterial or cerebrospinal fluid (CSF) flow, or vasculitis with appropriate clinical presentations. These include epilepsy, headache, impaired consciousness, orientation, cognition, focal neurological motor, sensory, or vegetative deficits, or visual impairment. CNS involvement is diagnosed on the clinical presentation, the epidemiological background, blood and CSF investigations, imaging studies, and sometimes biopsy. Treatment is based on various antihelminthic agents and, occasionally, surgery.