Primary cerebral cystic echinococcosis in a child from Roman countryside: Source attribution and scoping review of cases from the literature.

BACKGROUND: Human cystic echinococcosis (CE) is a zoonotic parasitic infection caused by the larval stage of the species belonging to the Echinococcus granulosus sensu lato (s.l.) complex. Parasitic cysts causing human CE are mainly localized in the liver and in the lungs. In a smaller number of cases, larvae may establish in any organ or tissue, including the central nervous system (CNS). Cerebral CE (CCE) is rare but poses serious clinical challenges. METHODS: This study presents a case of CCE in a child living in the countryside near Rome (Italy), along with a comparative molecular analysis of the isolated cyst specimens from the patient and sheep of local farms. We also systematically searched the literature to summarize the most relevant epidemiological and clinical aspects of this uncommon localization. FINDINGS: The comparative molecular analysis confirmed that the infection was caused by E. granulosus sensu stricto (s.s.) (G3 genotype), and most likely acquired in the family farm. The literature search identified 2,238 cases of CCE. In 80.51% of cases, brain was the only localization and single CCE cysts were present in 84.07% of cases. Mean patients' age was 20 years and 70.46% were children. Cyst rupture was reported in 12.96% and recurrence of CCE after treatment in 9.61% of cases. Permanent disability was reported in 7.86% of cases, while death occurred in 6.21%. In case series reporting all CE localization, CCE represented 1.5% of all CE cases. In the few reports that identified at molecular level the CCE cyst, E. granulosus s.s. was found in 40% and E. canadensis in 60% of cases. CONCLUSIONS: We report a rare case of CCE and evidenced the probable local origin of infection. The proportions of CE cases with uncommon localizations and with high impact on patients' lives have been globally neglected and should be included in the computation of the global burden of CE.

Clinical Characteristics and Treatment Outcome of Eosinophilic Meningoencephalitis in South Indian Children: Experience From a Prospective Registry.

BACKGROUND: To describe the clinical features and therapeutic outcomes of a prospective cohort of children with eosinophilic meningoencephalitis. METHODS: Children admitted with clinical features suggestive of meningitis along with cerebrospinal fluid (CSF) eosinophilia during the period of 14 years (2008 to 2021) were included. Their baseline characteristics, epidemiologic associations, and treatment outcomes were analyzed and compared with the previous studies. RESULTS: We identified 25 children (13 males) satisfying the inclusion criteria. The median age at presentation was 3.9 years (range 0.8 to 17 years); 68% were aged less than two years. Fourteen (56%) children had a history of exposure to snails. Most of them presented with fever, headache, irritability, lateral rectus palsy, and early papilledema. Symptoms started three to 42 days (median duration: 14 days) before admission to our center. All children had peripheral eosinophilia, which ranged from 9% to 41%. The mean CSF white blood cell count was 416/mm3 (range 50 to 1245 cells/mm3) with CSF eosinophilia ranging from 11% to 80%. Brain magnetic resonance imaging was done in 24 children and was normal in 15 (62.5%). Leptomeningeal enhancement was seen in two (8.3%) children, and other nonspecific changes were noted in seven (29.1%) children. All children recovered without any neurological deficits with a standard treatment regimen of albendazole and oral steroids. All were asymptomatic at the last follow-up. None of them had any recurrence during the follow-up period. CONCLUSION: We report one of the largest clinical series of children with eosinophilic meningoencephalitis from an endemic area of South India.

A clinical case report of Balamuthia granulomatous amoebic encephalitis in a non-immunocompromised patient and literature review.

BACKGROUND: Balamuthia granulomatous amoebic encephalitis (GAE) is a peculiar parasitic infectious disease of the central nervous system, about 39% of the infected Balamuthia GAE patients were found to be immunocompromised and is extremely rare clinically. The presence of trophozoites in diseased tissue is an important basis for pathological diagnosis of GAE. Balamuthia GAE is a rare and highly fatal infection for which there is no effective treatment plan in clinical practice. CASE PRESENTATION: This paper reports clinical data from a patient with Balamuthia GAE to improve physician understanding of the disease and diagnostic accuracy of imaging and reduce misdiagnosis. A 61-year-old male poultry farmer presented with moderate swelling pain in the right frontoparietal region without obvious inducement three weeks ago. Head computed tomography(CT) and magnetic resonance imaging(MRI) revealed a space-occupying lesion in the right frontal lobe. Intially clinical imaging diagnosed it as a high-grade astrocytoma. The pathological diagnosis of the lesion was inflammatory granulomatous lesions with extensive necrosis, suggesting amoeba infection. The pathogen detected by metagenomic next-generation sequencing (mNGS) is Balamuthia mandrillaris, the final pathological diagnosis was Balamuthia GAE. CONCLUSION: When a head MRI shows irregular or annular enhancement, clinicians should not blindly diagnose common diseases such as brain tumors. Although Balamuthia GAE accounts for only a small proportion of intracranial infections, it should be considered in the differential diagnosis.

Repurposed drug battles 'brain-eating' amoeba.

A drug for urinary tract infections may also treat Balamuthia mandrillaris.

Imaging of Central Nervous System Parasitic Infections.

Parasitic infections of the central nervous system (CNS) constitute a wide range of diseases, some quite prevalent across the world, some exceedingly rare. Causative parasites can be divided into two groups: unicellular protozoa and multicellular helminthic worms. This includes diseases such as neurotoxoplasmosis and neurocysticercosis, which represent a major cause of pathology among certain populations, and some more uncommon diseases, as primary amebic meningoencephalitis and neuroschistosomiasis. In this review, we focus on imaging manifestation and some helpful clinical and epidemiologic features of such conditions, providing radiologists with helpful information to identify and correctly diagnose the most common of those pathologies.

Higher Concentration of Taenia Antigens in the CSF is Related to Slight Ventricle Enlargement and Periventricular Neuronal Decrease in Young Rats

Purpose Experimental models might help understand the pathophysiology of neurocysticercosis-associated hydrocephalus. The present study aimed to compare the extent of hydrocephalus and tissue damage in rats with subarachnoid inoculation of different concentrations of Taenia crassiceps cyst proteins. Methods Sixty young rats were divided into two groups: low- and high-concentration groups. The animals in the low concentration group received 0.02ml of 2.4mg/ml T. crassiceps cyst proteins while those in the high concentration group received 0.02 ml of 11.6mg/ml T. crassiceps cyst proteins. The animals underwent magnetic resonance imaging at 1, 3, and 6 months postinoculation to assess the ventricle volume. Morphological assessment was performed at the end of the observation period. Results Repeated measures of ventricle volumes at 1, 3, and 6 months showed progressive enlargement of the ventricles. At 1 and 3 months, we observed no differences in ventricle volumes between the 2 groups. However, at 6 months, the ventricles were larger in the high concentration group (median » 3.86mm3, range: 2.37­12.68) compared with the low concentration group (median » 2.00mm3, range: 0.37­11.57), p » 0.003. The morphological assessment revealed a few inflammatory features in both groups. However, the density of oligodendrocytes and neurons within the periventricular region was lower in the high concentration group (5.18 versus 9.72 for oligodendrocytes and 15.69 versus 21.00 for neurons; p < 0.001 for both). Conclusion Our results suggest that, in rats, a higher concentration of T. crassiceps cyst proteins in the subarachnoid space could induce ventricle enlargement and reduce the number of neurons within the periventricular area.

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.

Toxocara-induced neural larva migrans (neurotoxocarosis) in rodent model hosts.

Neural larva migrans (NLM), or neurotoxocarosis, induced by Toxocara canis or Toxocara cati results from migrating and persisting larvae in the central nervous system of paratenic hosts, including humans. As the diagnosis of NLM in humans is not straightforward, most knowledge on the disease is derived from only a few published clinical cases. To improve our understanding of human NLM, studies on the pathogenesis and clinical symptoms in laboratory animal model systems are indispensable, and rodents have been accepted as the most appropriate model organisms for NLM. As research has mostly focused on neuroinvasive T. canis-larvae, information regarding the pathogenesis of T. cati-induced NLM remains scarce. This review summarises the current state of knowledge on neuroinvasion by both T. canis and T. cati in different rodent model hosts, the resulting behavioural changes, and histopathological alterations during the course of NLM as well as the potential molecular pathogenic mechanisms.

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.

Pathogenesis of cerebral toxocariasis and neurodegenerative diseases.

Toxocara canis belongs to one of zoonotic parasites that commonly infects canines worldwide, and its eggs in host faeces may contaminate the food, water, soil and their fur as well as the larvae entrapped in the granuloma can infect paratenic hosts including mice and humans. Survivability of T. canis embryonated eggs under moist, cool conditions may be as long as 2-4 years or more. In paratenic hosts such as mice and humans, T. canis L3 larvae neither moult, grow, nor replicate and will wander through a number of internal organs in humans so as to cause Th2-dominant pathology in various internal organs as leading to neurotoxocariasis (NT), ocular toxocariasis (OT), or visceral larva migrans (VLM). Although the systemic immune response to T. canis has been widely reported, the immune response in the brain has received little attention. Differential cytokine expression and other brain injury-associated biomarkers or neurodegeneration-associated factors have been observed in infected versus uninfected outbred and inbred mice. Preliminary data have also suggested a possible link between significant memory impairment and cytokine production associated with T. canis infection in the hippocampus which has been long recognised as being responsible for learning and memory functions. Notably, it remains an enigma concerning cerebral invasion by T. canis larvae rarely induces a recognisable neurological syndrome or its involvement in neuropathological disorders in humans. Exploration of the relationship between host and parasite in the brain may elucidate the cryptic symptoms of human cerebral toxocariasis, with patients presenting with mental retardation, epilepsy, neurodegeneration and other central nervous system (CNS) disorders.

Neurocognitive and neuropsychiatric effects of toxocariasis.

Caused by the neuroinvasive nematodes Toxocara canis and Toxocara cati, human toxocariasis has a worldwide distribution with seroprevalence in humans associated with low socioeconomic status and low educational attainment. Third-stage Toxocara larvae can invade human tissues, including the brain and spine, where they can result in encephalitis, meningitis, and inflammation. Toxocara infection in animal models has been associated with cognitive and behavioural changes. In humans, preliminary cross-sectional research suggests that Toxocara seropositivity is associated with worse cognitive function in children and adults. Additional preliminary cross-sectional findings suggest associations between Toxocara seropositivity and neuropsychiatric function, including schizophrenia and neurologic conditions such as epilepsy. Given the widespread distribution of human toxocariasis and early evidence suggesting that it can be associated with cognitive and neuropsychiatric function in humans, additional research regarding the effects of toxocariasis on the human brain is required.

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.

Nerve growth factor in the psychiatric brain.

The nerve growth factor (NGF) belongs to a family of proteins named neurotrophins, consisting of NGF, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), NT-4/5 and NT-6. NGF regulates a large number of physiological mechanisms that result in neurotrophic, metabotrophic and/or immunotrophic effects. Neurodegenerative diseases, including Alzheimer disease, psychiatric disorders (e.g. depression and schizophrenia) and brain parasitic infection have in common the effect of changing the brain levels of neurotrophins, in particular NGF. The contribution of both NGF and its receptor TrkA in such events and the recent promising results of NGF based therapies are here presented and discussed.

Neuroimaging of Emergent and Reemergent Infections.

Infectious diseases emerge and reemerge over the years, and many of them can cause neurologic disease. Several factors contribute to the emergence and reemergence of these conditions, including human population growth, an increase in international travel, the geographic expansion of recognized pathogens to areas where they were previously nonendemic, and greater contact with wild animal reservoirs. The antivaccination social movement has played an important role in the reemergence of infectious diseases, especially some viral conditions. The authors review different viral (arboviruses such as dengue, chikungunya, and Zika virus; enterovirus 71; measles; and influenza), bacterial (syphilis, Lyme disease, and listeriosis), and parasitic (Chagas disease) diseases, focusing primarily on their neurologic complications. Although there are several additional infectious diseases with central nervous system manifestations that could be classified as emergent or reemergent, those listed here are the most relevant from an epidemiologic standpoint and are representative of important public health issues on all continents. The infections caused by these pathogens often show a variety of neuroimaging patterns that can be identified at CT and MRI, and radiology is central to the diagnosis and follow-up of such conditions. Given the increasing relevance of emerging and reemerging infections in clinical practice and public health scenarios, radiologists should be familiar with these infections. Online supplemental material is available for this article. ©RSNA, 2019.

NFAT1 Regulates Ly6Chi Monocyte Recruitment to the CNS and Plays an Essential Role in Resistance to Toxoplasma gondii Infection.

Monocytes play key roles in the maintenance of homeostasis and in the control of the infection. Monocytes are recruited from the bone marrow to inflammatory sites and are essential for antimicrobial activity to limit tissue damage and promote adaptive T cell responses. Here, we investigated the role of Nuclear Factor of Activated T cells 1 (NFAT1) in the regulation of Ly6Chi inflammatory monocyte recruitment to the CNS upon T. gondii infection. We show that NFAT-1-deficient monocytes are unable to migrate to the CNS of T. gondii-infected mice. Moreover, NFAT1-/- mice are highly susceptible to chronic T. gondii infection due to a failure to control parasite replication in the CNS. The inhibition of Ly6Chi inflammatory monocyte recruitment to the CNS severely blocked CXCL10 production and consequently the migration of IFN-γ-producing CD4+ T cells. Moreover, the transfer of Ly6Chi monocytes to infected NFAT1-/- mice favored CD4+ T cell migration to the CNS and resulted in the inhibition of parasite replication and host defense. Together, these results demonstrated for the first time the contribution of NFAT1 to the regulation of Ly6Chi monocyte recruitment to the CNS and to resistance during chronic T. gondii infection.