Clinical Signs Of Neurologic Disease Research Articles

CT and MRI characterization of presumed persistent ossiculum terminale in dogs.

Anecdotally, during the review of CT and MRI studies of canine patientsincluding the cranial cervical spine, authors have identified a small osseous structure between the atlas (C1) and axis (C2) with no relevant clinical signs. This structure appeared comparable to a "persistent ossiculum terminale" in humans. The aim of this retrospective, multi-center, case series study was to describe the CT and MRI features of presumedpersistent ossiculum terminale in a group of dogs presented with unrelated medical conditions. Two databases (the imaging database of the teleradiology service VetCTSpecialists and the clinical database of the University of Vienna) were scrutinized by different approaches. Medical records of dogs that underwent imaging investigation (CT and/or MRI) that included the atlanto-axial junction were reviewed. Data collected included signalment, sex, breed, age, presenting symptoms, and final diagnosis. Eighteen dogs met the inclusion criteria. Mean age was 85 months (6-166) and breed variation was present. A total of 20 imaging studies were evaluated: CT was performed in 17 dogs; MRI in three dogs; two dogs had both MRI and CT performed. In all cases the presence of at least one small osseous body on the cranial aspect of the odontoid process compatible with a persistent ossiculum terminale was identified as a possible incidental finding without any overt clinical implications. Findings indicated that a small osseous body on the cranial aspect of the odontoid process (presumed persistent ossiculum terminale) in CT and MRI studies may be present in dogs with no clinical signs of neurologic disease.

Tick-borne encephalitis virus.

Tick-borne encephalitis (TBE) is caused by a neurotropic flavivirus, transmitted by the bite of Ixodes species tick vectors, and is increasing in incidence and expanding its geographical range throughout Eurasia and the Far East. Most infections are asymptomatic. However, between 2 and 30 % of cases may develop into severe neurological disease, long-term neurological sequelae or death. Diagnosis is based upon clinical signs of neurological disease and demonstration of virus-specific IgM and IgG antibodies. There is no specific antiviral treatment and supportive care is required for the various manifestations of disease. Vaccination is an effective way of preventing disease.

Japanese encephalitis virus infection in meerkats (Suricata suricatta)

Japanese encephalitis virus (JEV) infection has been recognized as a serious disease in humans. Wildlife animal infections due to JEV have not been well described. This study identified JEV infection in two deceased meerkats in Thailand, with clinical signs of neurological disease. Histopathology of brains revealed severe lymphoplasmacytic necrotizing meningoencephalitis, while similar inflammation was observed in the lung and liver. Partial JEV sequences were identified from the formalin-fixed paraffin-embedded-derived brain sections of two meerkats and were found to be genetically similar to a JEV strain detected in China but not from a local strain. Using immunohistochemistry, the virus was identified in neurons and glial cells, and also found in bronchial glands, Kupffer's cells in liver, lymphocytes in the spleen and pancreatic acini, which suggests extraneural infection. Transmission electron microscopy confirmed the presence of spheroid viral particles in the lungs. These findings may suggest that infection of extraneural organs in meerkats is similar to that described in JEV-infected humans. In conclusion, this study identified the first JEV infection in meerkats as an interesting case study. The JEV should be considered as an important differential diagnosis in meerkats with encephalitis. Further surveillance on JEV infection in meerkats and other wildlife species in a large cohort is needed in the future study.

Mesenchymal stem cell transplantation into the spinal cord of healthy adult horses undergoing cervical ventral interbody fusion.

To determine the feasibility of umbilical cord-derived mesenchymal stem cell (UC-MSC) transplantation into the cervical spinal cord of horses by using fluoroscopy with or without endoscopic guidance and to evaluate the neurological signs and tissue reaction after injection. Experimental study. Eight healthy adult horses with no clinical signs of neurological disease. After cervical ventral interbody fusion (CVIF), ten million fluorescently labeled allogeneic UC-MSC were injected into the spinal cord under endoscopic and fluoroscopic guidance (n=5) or fluoroscopic guidance only (n=3). Postoperative neurological examinations were performed, and horses were humanely killed 48 hours (n=4) or 14 days (n=4) postoperatively. Spinal tissues were examined after gross dissection and with bright field and fluorescent microscopy. Needle endoscopy of the cervical canal by ventral approach was associated with intraoperative spinal cord puncture (2/5) and postoperative ataxia (3/5). No intraoperative complications occurred, and one (1/3) horse developed ataxia with cell transplantation under fluoroscopy alone. Umbilical cord-derived MSC were associated with small vessels and detected up to 14 days in the spinal cord. Demyelination was observed in six of eight cases. Fluoroscopically guided intramedullary UC-MSC transplantation during CVIF avoids spinal cord trauma and decreases risk of ataxia from endoscopy. Umbilical cord-derived MSC persist in the spinal cord for up to 14 days. Cell injection promotes angiogenesis and induces demyelination of the spinal tissue. Umbilical cord-derived MSC transplantation into the spinal cord during CVIF without endoscopy is recommended for future evaluation of cell therapy in horses affected by cervical vertebral compressive myelopathy.

Evaluation of Antemortem Diagnostic Techniques in Goats Naturally Infected With Scrapie.

Scrapie is a naturally occurring transmissible spongiform encephalopathy (TSE) that affects sheep and goats. Sheep and goats can be infected with scrapie as lambs or kids via contact with the placenta or placental fluids, or from ingestion of prions shed in the environment and/or bodily fluids (e.g., saliva, urine, and feces). Like other TSEs, scrapie is generally not diagnosed before extensive and irreversible brain damage has occurred. Therefore, a reliable method to screen animals may facilitate diagnosis. Additionally, while natural scrapie in sheep has been widely described, naturally acquired goat scrapie is less well-characterized. The purpose of this study was to better understand natural goat scrapie in regard to disease phenotype (i.e., incubation period, clinical signs, neuroanatomical deposition patterns of PrPSc, and molecular profile as detected by Western blot) and to evaluate the efficacy of antemortem tests to detect scrapie-positive animals in a herd of goats. Briefly, 28 scrapie-exposed goats were removed from a farm depopulated due to previous diagnoses of scrapie on the premises and observed daily for 30 months. Over the course of the observation period, antemortem biopsies of recto-anal mucosa-associated lymphoid tissue (RAMALT) were taken and tested using immunohistochemistry and real-time quaking-induced conversion (RT-QuIC), and retinal thickness was measured in vivo using optical coherence tomography (OCT). Following the observation period, immunohistochemistry and Western blot were performed to assess neuroanatomical deposition patterns of PrPSc and molecular profile. Our results demonstrate that antemortem rectal biopsy was 77% effective in identifying goats naturally infected with scrapie and that a positive antemortem rectal biopsy was associated with the presence of clinical signs of neurologic disease and a positive dam status. We report that changes in retinal thickness are not detectable over the course of the observation period in goats naturally infected with scrapie. Finally, our results indicate that the accumulation of PrPSc in central nervous system (CNS) and non-CNS tissues is consistent with previous reports of scrapie in sheep and goats.

IL-22 hinders antiviral T cell responses and exacerbates ZIKV encephalitis in immunocompetent neonatal mice

BackgroundThe Zika virus (ZIKV) outbreak that occurred in multiple countries was linked to increased risk of nervous system injuries and congenital defects. However, host immunity- and immune-mediated pathogenesis in ZIKV infection are not well understood. Interleukin-22 (IL-22) is a crucial cytokine for regulating host immunity in infectious diseases. Whether IL-22 plays, a role in ZIKV infection is unknown.MethodsThe cellular source of IL-22 was identified in IFNAR-/- mice and wild-type (WT) neonatal mice during ZIKV infection. To determine the role of IL-22, we challenged 1-day-old WT and IL-22-/- mice with ZIKV and monitored clinical manifestations. Glial cell activation in the brain was assessed by confocal imaging. ZIKV-specific CD8+ T cell responses in both the spleen and brain were analyzed by flow cytometry. In addition, glial cells were cultured in vitro and infected with ZIKV in the presence of IL-22, followed by the evaluation of cell proliferation, cytokine expression, and viral loads.ResultsWe found that γδ T cells were the main source of IL-22 during ZIKV infection in both the spleen and brain. WT mice began to exhibit weight loss, staggered steps, bilateral hind limb paralysis, and weakness at 10 days post-infection (dpi) and ultimately succumbed to infection at 16–19 dpi. IL-22 deficiency lessened weight loss, moderated the systemic inflammatory response, and greatly improved clinical signs of neurological disease and mortality. ZIKV infection also induced the activation of microglia and astrocytes in vitro. Additional analysis demonstrated that the absence of IL-22 resulted in reduced activation of microglia and astrocytes in the cortex. Although IL-22 displayed a negligible effect on glial cells in vitro, IL-22-/- mice mounted more vigorous ZIKV-specific CD8+ T cell responses, which led to a more effective control of ZIKV in the brain.ConclusionsOur data revealed a pathogenic role of IL-22 in ZIKV encephalitis.

Evaluation of cell-free DNA as a diagnostic marker in cerebrospinal fluid of dogs.

To determine whether cell-free DNA (cfDNA) was detectable in CSF samples from dogs, whether CSF sample volume impacted CSF cfDNA concentration measurement, and whether CSF cfDNA concentration was associated with CNS disease category or CSF RBC count (RBCC), nucleated cell count (NCC), or protein concentration, which could aid in the diagnosis of neurologic diseases in dogs. 80 CSF samples collected from dogs with (n = 60) and without (20) clinical neurologic disease between February 2017 and May 2018. Results for CSF RBCC, NCC, protein concentration, and cfDNA concentration were compared across CSF groups established on the basis of whether they were obtained from dogs with (case groups) or without (control group) clinical signs of neurologic disease In addition, 5 paired CSF samples representing large (3.0-mL) and small (0.5-mL) volumes, were used to evaluate whether sample volume impacted measurement of CSF cfDNA concentration. cfDNA was detected in 76 of the 80 (95%) CSF samples used to evaluate parameters across disease categories and in all 5 of the paired samples used to evaluate whether sample volume impacted cfDNA quantification. There were no substantial differences in cfDNA concentrations identified between groups (on the basis of disease category or sample volume), and the CSF cfDNA concentration did not meaningfully correlate with CSF RBCC, NCC, or protein concentration. Although results indicated that the CSF cfDNA concentration could not be used to differentiate between categories of neurologic disease in dogs of the the present study, further investigation is warranted regarding the use of CSF analysis, including sequencing specific cfDNA mutations, for diagnosing and monitoring neurologic disease in dogs.

A Baylisascaris Outbreak in Fox Squirrels (Sciurus niger) and Subsequent Detection of Francisella tularensis in Kansas, USA

Thorough epidemiologic investigations of wildlife mortality events are often challenging, in part because of the dynamic variables involved. In May 2011, six fox squirrels (Sciurus niger) in Clinton State Park, Kansas, US were euthanized after exhibiting clinical signs of neurologic disease. Postmortem examination of two squirrels revealed that these individuals died of Baylisascaris larva migrans, which resulted in meningoencephalitis and variable pneumonia and myocarditis. Fecal flotation of raccoon (Procyon lotor) feces collected in the area revealed Baylisascaris sp. ova, presumably Baylisascaris procyonis, in one of nine samples. Additional fox squirrel carcasses were submitted for diagnostic evaluation from eastern Kansas for 1 yr following the Baylisascaris sp. outbreak. This monitoring unexpectedly resulted in the detection of Francisella tularensis, the zoonotic pathogen that causes tularemia, in two fox squirrels. The increased attention to fox squirrel mortalities prompted by the outbreak of Baylisascaris sp. larva migrans revealed cases of tularemia that may not have been otherwise detected. Although F. tularensis is endemic in Kansas, the current distribution and prevalence of B. procyonis in raccoons and other hosts in Kansas are poorly understood. This yearlong mortality investigation illustrated the importance of wildlife health monitoring as a means of assessing public health risks, especially during unusual wildlife mortality events.

Clinical signs, profound acidemia, hypoglycemia, and hypernatremia are predictive of mortality in 1,400 critically ill neonatal calves with diarrhea.

Profound acidemia impairs cellular and organ function and consequently should be associated with an increased risk of mortality in critically ill humans and animals. Neonatal diarrhea in calves can result in potentially serious metabolic derangements including profound acidemia due to strong ion (metabolic) acidosis, hyper-D-lactatemia, hyper-L-lactatemia, azotemia, hypoglycemia, hyperkalemia and hyponatremia. The aim of this retrospective study was to assess the prognostic relevance of clinical and laboratory findings in 1,400 critically ill neonatal calves with diarrhea admitted to a veterinary teaching hospital. The mortality rate was 22%. Classification tree analysis indicated that mortality was associated with clinical signs of neurologic disease, abdominal emergencies, cachexia, orthopedic problems such as septic arthritis, and profound acidemia (jugular venous blood pH < 6.85). When exclusively considering laboratory parameters, classification tree analysis identified plasma glucose concentrations < 3.2 mmol/L, plasma sodium concentrations ≥ 151 mmol/L, serum GGT activity < 31 U/L and a thrombocyte count < 535 G/L as predictors of mortality. However, multivariable logistic regression models based on these laboratory parameters did not have a sufficiently high enough sensitivity (59%) and specificity (79%) to reliably predict treatment outcome. The sensitivity and specificity of jugular venous blood pH < 6.85 were 11% and 97%, respectively, for predicting non-survival in this study population. We conclude that laboratory values (except jugular venous blood pH < 6.85) are of limited value for predicting outcome in critically ill neonatal calves with diarrhea. In contrast, the presence of specific clinical abnormalities provides valuable prognostic information.

Neurofilament light as an immune target for pathogenic antibodies.

Antibodies to neuronal antigens are associated with many neurological diseases including paraneoplastic neurological disorders, epilepsy, amyotrophic lateral sclerosis and multiple sclerosis. Immunization with neuronal antigens such as neurofilament light (NF-L), a neuronal intermediate filament in axons, has been shown to induce neurological disease and spasticity in mice. Also, although antibodies to NF-L are widely used as surrogate biomarkers of axonal injury in amyotrophic lateral sclerosis and multiple sclerosis, it remains to be elucidated if antibodies to NF-L contribute to neurodegeneration and neurological disease. To address this, we examined the pathogenic role of antibodies directed to NF-L invitro using spinal cord co-cultures and invivo in experimental autoimmune encephalomyelitis (EAE) and optic neuritis animal models of multiple sclerosis. Here we show that peripheral injections of antibodies to NF-L augmented clinical signs of neurological disease in acute EAE, increased retinal ganglion cell loss in experimental optic neuritis and induced neurological signs following intracerebral injection into control mice. The pathogenicity of antibodies to NF-L was also observed in spinal cord co-cultures where axonal loss was induced. Taken together, our results reveal that as well as acting as reliable biomarkers of neuronal damage, antibodies to NF-L exacerbate neurological disease, suggesting that antibodies to NF-L generated during disease may also be pathogenic and play a role in the progression of neurodegeneration.

Neuropathological survey reveals underestimation of the prevalence of neuroinfectious diseases in cattle in Switzerland

Neuroinfectious diseases in livestock represent a severe threat to animal health, but their prevalence is not well documented and the etiology of disease often remains unidentified. The aims of this study were to generate baseline data on the prevalence of neuroinfectious diseases in cattle in Switzerland by neuropathological survey, and to identify disease-associated pathogens. The survey was performed over a 1-year period using a representative number of brainstem samples (n=1816) from fallen cattle. In total, 4% (n=73) of the animals had significant lesions, the most frequent types of which were indicative of viral (n=27) and bacterial (n=31) etiologies. Follow-up diagnostics by immunohistochemistry, PCR protocols and next-generation sequencing identified infection with Listeria monocytogenes (n=6), ovine herpesvirus 2 (n=7), bovine astrovirus CH13 (n=2), bovine herpesvirus 6 (n=6), bovine retrovirus CH15 (n=2), posavirus 1 (n=2), and porcine astroviruses (n=2). A retrospective questionnaire-based investigation indicated that animals’ owners observed clinical signs of neurological disease in about one-third of cases with lesions, which was estimated to correspond to approximately 85 cases per year in the adult fallen cattle population in Switzerland. This estimate stands in sharp contrast to the number of cases reported to the authorities and reveals a gap in disease surveillance. Systematic neuropathological examination and follow-up molecular testing of neurologically diseased cattle could significantly enhance the efficiency of disease detection for the purposes of estimating the prevalence of endemic diseases, identifying new or re-emerging pathogens, and providing “early warnings” of disease outbreaks.

Atypical scrapie in Australia.

Since its initial detection in Norway in 1998, atypical scrapie ('atypical/Nor98 scrapie') has been reported in sheep in the majority of European countries (including in regions free of classical scrapie) and in the Falkland Islands, the USA, Canada, New Zealand and Australia. The diagnosis in Australia of atypical scrapie in four Merino and one Merino-cross sheep showing clinical signs of neurological disease was based on the detection of grey matter neuropil vacuolation (spongiform change) in the brain (particularly in the molecular layer of the cerebellar cortex) and associated abnormal prion protein (PrPSc ) deposition in both grey and white matter. Changes were minimal in the caudal brainstem, the predilection site for lesions of classical scrapie. The distinctive lesion profile of atypical scrapie in these five sheep highlights the diagnostic importance of routine histological evaluation of the cerebellum for evidence of neuropil vacuolation and associated PrPSc deposition in adult sheep with suspected neurological disease.

Neurological Diseases of Rabbits and Rodents

Clinical signs of neurological disease, such as head tilt, hind limb paresis or paralysis, seizures, and muscle weakness, are commonly encountered in pet rabbits, and in the authors׳ experience, less often in rodent species. Moreover, localisation of neurological lesions and establishment of a definitive diagnosis can be challenging for any of the exotic small mammal species. In many rabbit and rodent cases, distinguishing neurological disease from musculoskeletal disease is difficult. The parasitic disease encephalitozoonosis is commonly diagnosed in pet rabbits; in both rabbits and rodents, bacterial infections are also a common underlying cause of neurological disease. Other causes of neurological diseases that adversely affect pet rabbits and rodents include toxins, trauma, metabolic and degenerative disorders, viral infections, neoplasia, and hereditary abnormalities.

Cerebrospinal fluid eosinophilia is a sensitive and specific test for the diagnosis of Parelaphostrongylus tenuis in camelids in the northeastern United States

Aberrant migration of Parelaphostrongylus tenuis in camelids results in neurologic deficits, recumbency, and sometimes death. An antemortem diagnosis of P. tenuis in camelids is typically based upon the presence of characteristic asymmetric neurologic deficits, known exposure to white-tailed deer, cerebrospinal fluid (CSF) eosinophilia, and response to treatment. The diagnostic accuracy of CSF eosinophil percentage for the diagnosis of P. tenuis in camelids has not been critically examined. The objective of the current study was to determine the sensitivity (Se) and specificity (Sp) of CSF eosinophil percentage, CSF eosinophil concentration, total nucleated cell concentration, and protein concentration for the antemortem diagnosis of P. tenuis. Medical records of camelids admitted to Cornell University with clinical signs of neurologic disease, CSF analysis, and necropsy were examined from January 2000 through December 2009. Se and Sp were determined by receiver operating characteristic curves in camelids diagnosed with P. tenuis (n = 13) or other conditions (n = 24) based on postmortem examination. More than 17% of eosinophils in CSF had a Se of 85% and Sp of 92% for P. tenuis diagnosis (area under the curve [AUC]: 0.87; SE AUC: 0.07; P < 0.0001; 95% confidence interval [CI] AUC: 0.72-0.96), and >1.4 eosinophils/µl of CSF had a Se of 85% and Sp of 96% (AUC: 0.9; SE AUC: 0.06; P < 0.0001; 95% CI AUC: 0.76-0.97). Cerebrospinal fluid eosinophil percentage and concentration are sensitive and specific methods for diagnosing P. tenuis antemortem in camelids residing in regions endemic to white-tailed deer.

Experimental infection with neuropathogenic equid herpesvirus type 1 (EHV-1) in adult horses

Equid herpesvirus type 1 (EHV-1)-associated myeloencephalopathy (EHM) may follow an infection with the virus in horses. This study tested three hypotheses: (1) a large inhaled dose of a neuropathogenic EHV-1 strain would induce a cell-associated viraemia in all infected horses; (2) neurological disease will only occur in viraemic horses, and (3) the cerebrospinal fluid (CSF) composition following EHV-1 viraemia will be an indicator for EHM. Four EHV-1 seronegative horses were inoculated with EHV-1 by inhalation. Three developed clinical signs of neurological disease, which were mild in two horses and lacking typical EHM histopathological findings, but moderately severe in the third horse. This latter animal was the only one found to be viraemic, with xanthochromic CSF and spinal cord histopathology findings characteristic of EHM. This study showed that cell-associated viraemia was not guaranteed, despite a large-dose inoculation with EHV-1, yet viraemia was probably a pre-requisite for subsequent development of EHM. The histopathological changes used to confirm EHM may be predicted from CSF analysis.

Periventricular Spread of Primary Central Nervous System T-cell Lymphoma in a Cat

A 9-year-old domestic shorthaired cat with clinical signs of neurological disease was determined to have primary T-cell lymphoma of the central nervous system (CNS) on necropsy examination. Microscopically, neoplastic lymphocytes were distributed in the CNS parenchyma bilaterally around the cerebral ventricles, third ventricle, mesencephalic aqueduct, fourth ventricle and central canal of the spinal cord. The neoplastic infiltration was associated with complete loss of ependymal cells and marked astrocytosis. A large, solitary neoplastic lesion was present in the parenchyma around the central canal of the spinal cord at the level of the 13th thoracic vertebra. Immunohistochemically, the majority of neoplastic cells expressed CD3 and many also labelled for proliferating cell nuclear antigen (PCNA) and Ki-67. This is, to our knowledge, the first report of periventricular spread of primary CNS T-cell lymphoma in animals.

Meningoencephalitis in an Adult Cow Due to Mortierella Wolfii

A 7-year-old dairy cow presented with clinical signs of neurologic disease. Despite treatment with penicillin, the cow died 36 hours after initial presentation. Necropsy examination revealed multiple foci of hemorrhage within the cerebrum and thickened meninges. Additionally, endometritis and consolidation of approximately 30% of both lungs was observed. Histology revealed necrotizing vasculitis, infarction, and hemorrhage within sections of the brain, uterus, and lung. Large numbers of intralesional fungal hyphae were visible. Because only formalin-fixed tissue was available, polymerase chain reaction was used to make an etiologic diagnosis of Mortierella wolfii.

Central Nervous System Dysfunction Associated With Rocky Mountain Spotted Fever Infection in Five Dogs

Five dogs from the northeastern United States were presented with clinical signs of neurological disease associated with Rocky Mountain spotted fever (RMSF) infection. Four of the five dogs had vestibular system dysfunction. Other neurological signs included paresis, tremors, and changes in mentation. All of the dogs had an elevated indirect fluorescent antibody titer or a positive semiquantitative enzyme screening immunoassay titer for Rickettsia rickettsii at the time of presentation. Although a higher mortality rate has been reported for dogs with neurological symptoms and RMSF infection, all of the dogs in this study improved with appropriate medical therapy and supportive care.

Immunodetection of disease-associated mutant PrP, which accelerates disease in GSS transgenic mice

The absence of infectivity-associated, protease-resistant prion protein (PrP(Sc)) in the brains of spontaneously sick transgenic (Tg) mice overexpressing PrP linked to Gerstmann-Sträussler Scheinker syndrome, and the failure of gene-targeted mice expressing such PrP to develop disease spontaneously, challenged the concept that mutant PrP expression led to spontaneous prion production. Here, we demonstrate that disease in overexpressor Tg mice is associated with accumulation of protease-sensitive aggregates of mutant PrP that can be immunoprecipitated by the PrP(Sc)-specific monoclonal antibody designated 15B3. Whereas Tg mice expressing multiple transgenes exhibited accelerated disease when inoculated with disease-associated mutant PrP, Tg mice expressing mutant PrP at low levels failed to develop disease either spontaneously or following inoculation. These studies indicate that inoculated mutant PrP from diseased mice promotes the aggregation and accumulation of pre-existing pathological forms of mutant PrP produced as a result of transgene overexpression. Thus, while pathological mutant PrP possesses a subset of PrP(Sc) characteristics, we now show that the attribute of prion transmission suggested by previous studies is more accurately characterized as disease acceleration.

Infection of Immunodeficient Horses withSarcocystis neuronaDoes Not Result in Neurologic Disease

Equine protozoal myeloencephalitis is a progressive neurologic disease of horses most commonly caused by infection with the apicomplexan parasite Sarcocystis neurona. Factors affecting neuroinvasion and neurovirulence have not been determined. We investigated the pathogenesis of infection with S. neurona in horses with severe combined immune deficiency (SCID). Two immunocompetent (IC) Arabian horses and two Arabian horses with SCID were infected orally with 5 x 10(5) sporocysts of S. neurona. Four IC horses and one SCID horse were infected intravenously (i.v.) with 5 x 10(8) merozoites of the WSU-1 isolate of S. neurona. Despite prolonged parasitemia and persistent infection of visceral tissues (skeletal muscle, cardiac muscle, lung, liver, and spleen) as demonstrated by PCR and culture, SCID horses did not develop neurologic signs after oral or i.v. infection. S. neurona was undetectable in the neuronal tissues of SCID horses by either PCR, immunohistochemistry, or culture. In contrast, although parasitemia was undetectable in orally infected IC horses and of only short duration in i.v. infected IC horses, four of six IC horses developed neurologic signs. S. neurona was detectable by PCR and/or culture of neural tissue but not visceral tissue of IC horses with neurologic disease. Infected SCID horses are unable to clear S. neurona from visceral tissues, but the infection does not result in neurologic signs; in contrast, IC horses rapidly control parasitemia and infection of visceral tissues but frequently experience neuroinvasion and exhibit clinical signs of neurologic disease.