Signs Of Neurological Disease Research Articles

A Homozygous KCNJ10 Mutation in Jack Russell Terriers and Related Breeds with Spinocerebellar Ataxia with Myokymia, Seizures, or Both

BackgroundJuvenile‐onset spinocerebellar ataxia has been recognized in Jack Russell Terriers and related Russell group terriers (RGTs) for over 40 years. Ataxia occurs with varying combinations of myokymia, seizures, and other signs of neurologic disease. More than 1 form of the disease has been suspected.Hypothesis/ObjectivesThe objective was to identify the mutation causing the spinocerebellar ataxia associated with myokymia, seizures, or both and distinguish the phenotype from other ataxias in the RGTs.Animals DNA samples from 16 RGTs with spinocerebellar ataxia beginning from 2 to 12 months of age, 640 control RGTs, and 383 dogs from 144 other breeds along with the medical records of affected dogs were studied.MethodsThis case‐control study compared the frequencies of a KCNJ10 allele in RGTs with spinocerebellar ataxia versus control RGTs. This allele was identified in a whole‐genome sequence of a single RGT with spinocerebellar ataxia and myokymia by comparison to whole‐genome sequences from 81 other canids that were normal or had other diseases.ResultsA missense mutation in the gene coding for the inwardly rectifying potassium channel Kir4.1 (KCNJ10:c.627C>G) was significantly (P < .001) associated with the disease. Dogs homozygous for the mutant allele all had spinocerebellar ataxia with varying combinations of myokymia and seizures.Conclusions and Clinical ImportanceIdentification of the KCNJ10 mutation in dogs with spinocerebellar ataxia with myokymia, seizures, or both clarifies the multiple forms of ataxia seen in these breeds and provides a DNA test to identify carriers.

Gastroparesis and Ischemic Gastric Ulcers in a Patient with Rheumatoid Arthritis Receiving Adalimumab Treatment

Case: A 57-year-old woman with rheumatoid arthritis (treated with adalimumab for the past 8 years) presented with 6 months history of left sided abdominal pain, nausea, vomiting, 15 pounds in 6 months, painless numbness in her feet, orthostatic hypotension and sweating. She did not have active joint symptoms. A 4-hour gastric emptying was low (50 %;normal: 84-98%). Upper endoscopy revealed multiple gastric ulcers and mottled appearing duodenum with biopsies showing ischemia. Ultrasound with Doppler, MRI and CT scan of the abdomen were unremarkable with no evidence of mesenteric artery stenosis. Electromyography demonstrated axonal sensorimotor peripheral neuropathy (PN). This finding was not consistent with PN from rheumatoid vasculitis. Autonomic reflex testing revealed autonomic dysfunction with impairment in cardiovagal and adrenergic function. The work-up for metabolic causes and malignancy associated PN were negative. She was diagnosed with PN with an autonomic component and gastroparesis. It was thought that adalimumab may have caused the autonomic neuropathy which manifested as gastroparesis and ischemic ulcers of the upper gut. The adalimumab was stopped. Her symptoms that she previously had, such as sweating with epigastric pain and weight loss, had improved. Follow-up endoscopy 3 months later showed resolution of gastric ulcers and repeat biopsies were normal and negative for ischemia. Discussion: Neurological events associated with adalimumab are exceedingly rare, developed in 0.1% of patients. To our knowledge, our case is the first reported of autonomic neuropathy, gastroparesis and ischemic gastric ulcers with adalimumab use. In the absence of mesenteric stenosis, we postulate that the ischemia was caused by hypotension secondary to autonomic insufficiency. Most cases of drug-induced PN improve over a period of months after withdrawal of TNF- α antagonists. This case highlights the importance of monitoring for symptoms and signs of neurologic disease in patients being treated with TNF-α antagonists.

Prevalence of antibodies toSarcocystis neuronaandNeospora hughesiin horses from Mexico

Equine protozoal myeloencephalitis (EPM) is a debilitating disease of horses caused by Sarcocystis neurona and Neospora hughesi. Sera from 495 horses in Durango State, Mexico were tested for anti-protozoal antibodies using enzyme-linked immunosorbent assays (ELISAs) based on major surface antigens of these two parasites. Antibodies to S. neurona were detected in 240 (48.5%) of the 495 horse sera tested with the rSnSAG2/4/3 trivalent ELISA. Multivariate analysis showed that exposure to S. neurona was associated with age, feeding grains and crops, and small herd size. Antibodies to N. hughesi were found in 15 (3.0%) of the 495 horse sera tested with the rNhSAG1 ELISA and confirmed by Western blot of N. hughesi tachyzoite antigen. This is the first report of S. neurona and N. hughesi exposure in horses in Mexico, and it affirms that EPM should be in the differential diagnosis for horses exhibiting signs of neurologic disease in this country.

Tawny frogmouths and brushtail possums as sentinels for Angiostrongylus cantonensis, the rat lungworm

The objective of this study was to determine the prevalence of angiostrongylosis in tawny frogmouths (Podargus strigoides) and brushtail possums (Trichosurus vulpecula) with signs of neurological disease, and to describe the clinicopathological features of angiostrongylosis in both species. Tawny frogmouths and brushtail possums with signs of neurological disease were sampled from the Sydney metropolitan area between October 1998 and June 2010. Samples from 100 tawny frogmouths and 31 brushtail possums from the Australian Registry of Wildlife Health (ARWH), the Wildlife Assistance and Information Foundation (WAIF) and Wildlife Health and Conservation Centre (WHCC), University of Sydney were examined. Histological examinations of the brain, spinal cord and other available tissues were used to characterize the disease responsible for each animal's clinical signs. Of the 100 tawny frogmouths with neurological disease examined, angiostrongylosis was considered responsible in 80 (80%), traumatic injury in 17 (17%), protozoal infection in 3 (3%) and other diseases in 2 (2%) and the cause of clinical signs was unknown in 10 (10%). Eleven tawny frogmouths presenting with neurological signs associated with head trauma had concurrent angiostrongylosis. Of the 31 brushtail possums, Wobbly Possum Syndrome (WPS) was diagnosed in 21 (68%), angiostrongylosis in 4 (13%) and other diseases in the remaining 6 (19%). Angiostrongylosis was overrepresented in hand reared juvenile possums. Cases of angiostrongylosis in tawny frogmouths followed a strong seasonal pattern peaking through late summer and autumn. The results confirm that Angiostrongylus cantonensis is endemic in Sydney, Australia and that tawny frogmouths could be important sentinels for this zoonotic parasite.

Stage progression and neurological symptoms in Trypanosoma brucei rhodesiense sleeping sickness: role of the CNS inflammatory response.

BackgroundHuman African trypanosomiasis progresses from an early (hemolymphatic) stage, through CNS invasion to the late (meningoencephalitic) stage. In experimental infections disease progression is associated with neuroinflammatory responses and neurological symptoms, but this concept requires evaluation in African trypanosomiasis patients, where correct diagnosis of the disease stage is of critical therapeutic importance.Methodology/Principal FindingsThis was a retrospective study on a cohort of 115 T.b.rhodesiense HAT patients recruited in Eastern Uganda. Paired plasma and CSF samples allowed the measurement of peripheral and CNS immunoglobulin and of CSF cytokine synthesis. Cytokine and immunoglobulin expression were evaluated in relation to disease duration, stage progression and neurological symptoms. Neurological symptoms were not related to stage progression (with the exception of moderate coma). Increases in CNS immunoglobulin, IL-10 and TNF-α synthesis were associated with stage progression and were mirrored by a reduction in TGF-β levels in the CSF. There were no significant associations between CNS immunoglobulin and cytokine production and neurological signs of disease with the exception of moderate coma cases. Within the study group we identified diagnostically early stage cases with no CSF pleocytosis but intrathecal immunoglobulin synthesis and diagnostically late stage cases with marginal CSF pleocytosis and no detectable trypanosomes in the CSF.ConclusionsOur results demonstrate that there is not a direct linkage between stage progression, neurological signs of infection and neuroinflammatory responses in rhodesiense HAT. Neurological signs are observed in both early and late stages, and while intrathecal immunoglobulin synthesis is associated with neurological signs, these are also observed in cases lacking a CNS inflammatory response. While there is an increase in inflammatory cytokine production with stage progression, this is paralleled by increases in CSF IL-10. As stage diagnostics, the CSF immunoglobulins and cytokines studied do not have sufficient sensitivity to be of clinical value.

Glucocerebrosidase mutations alter the endoplasmic reticulum and lysosomes in Lewy body disease.

Lewy body disease (LBD) development is enhanced by mutations in the GBA gene coding for glucocerebrosidase (GCase). The mechanism of this association is thought to involve an abnormal lysosomal system and we therefore sought to evaluate if lysosomal changes contribute to the pathogenesis of idiopathic LBD. Analysis of post-mortem frontal cortex tissue from 7 GBA mutation carriers with LBD, 5 GBA mutation carriers with no signs of neurological disease and human neural stem cells exposed to a GCase inhibitor was used to determine how GBA mutation contributes to LBD. GBA mutation carriers demonstrated a significantly reduced level of GCase protein and enzyme activity and retention of glucocerebrosidase isoforms within the endoplasmic reticulum (ER). This was associated with enhanced expression of the lysosomal markers LAMP1 and LAMP2, though the expression of ATP13A2 and Cathepsin D was reduced, along with the decreased activity of Cathepsin D. The ER unfolded protein response (UPR) regulator BiP/GRP78 was reduced by GBA mutation and this was a general phenomenon in LBD. Despite elevation of GRP94 in LBD, individuals with GBA mutations showed reduced GRP94 expression, suggesting an inadequate UPR. Finally, human neural stem cell cultures showed that inhibition of GCase causes acute reduction of BiP, indicating that the UPR is affected by reduced glucocerebrosidase activity. The results indicate that mutation in GBA leads to additional lysosomal abnormalities, enhanced by an impaired UPR, potentially causing α-synuclein accumulation.

Symmetry in Infancy: Analysis of Motor Development in Autism Spectrum Disorders

Motor asymmetry, defined as the lack of symmetry in movements or postures, is often observed briefly in many typically developing children. However, if such asymmetry persists, it may be a sign of neurological disease. Recent studies have suggested that motor asymmetries may be an early symptom of Autism Spectrum Disorders (ASD). ASD involve a range of social, cognitive, and behavioral problems, at different degrees of functioning, which are thought to be the final common pathway of multiple etiological mechanisms. Furthermore, early identification of ASD has been recognized as a critical aspect for treatment. Our study aims to analyze symmetry in the motor milestones of infants with ASD compared with typically developing infants (TD) or infants with other developmental delay (DD) during the first year of life. Our results highlight that there are different patterns of motor symmetry in the groups. In particular, infants with ASD scored significantly poorer (higher levels of asymmetry) then the TD and DD infants. We also identified two subgroups of infants with ASD, one with a typical level and the other with a lower level of motor functioning. Implications of the study for diagnosis and treatment are described.

Cerebrospinal Fluid Flow Cytometry Analysis in Newly Diagnosed Aggressive Non-Hodgkin Lymphomas at High Risk for Leptomeningeal Disease: Result of a Multicentric Prospective Italian Study.

Abstract 2919Poster Board II-895 Background:Flow cytometry (FCM) assessment of cerebrospinal fluid (CSF) has recently been known to increase the rate of positivity of occult leptomeningeal disease (LD) in comparison to conventional cytologic examination (CC). However it's still unknown its prognostic value. Patients and methods: The aim of this study was to compare CC vs FCM in a large cohort of patients with newly diagnosed aggressive NHL at high risk for LD (diffuse large B-cell lymphoma (DLBCL) IPI 2-3 and elevated LDH with at least two extranodal sites or with bone marrow, testis, paranasal sinuses, orbit or paravertebral involvement; Burkitt lymphoma (BL); blastoid variant of mantle cell lymphoma (B-MCL); B-cell precursor lymphoblastic lymphoma (B-LL); HIV+ aggressive lymphoma patients). All patients were required to have no evidence or signs of neurological disease. All patients received intrathecal standard prophylactic therapy with 12 mg of methothrexate except for BL that were given prophylaxis with 50 mg of liposomial aracytin for a total of 4 doses. CFS samples were analysed both with CC and FCM. The incidence of positive test for occult LD with FCM and CC was compared using the McNemar test for paired data. Results:Between August 2004 and June 2008, a total of 159 consecutive patients were enrolled in 11 Italian centres and underwent evaluation of CSF. Out of these, 128 patients (80%) were considered at high risk of occult LD. Clinical characteristics were: median age 53 years (IQR:43-62); DLBCL 96 patients (75%); BL 21 pts (16%); B-MCL 6 pts (5%); B-LL 5 pts (4%); 26 pts (20%) were HIV positive. FCM was able to detect a clonal population in 17 out of 128 patients (13%) whereas CC detected abnormal cells only among 7 pts (5%)(p= 0.0002). Therefore, 10 patients (8%) were discordant: FCM+/CC-. Among the 128 patients, there was no association between the CFS total protein, glucose level and the presence of positive analysis of FCM, whereas the difference between the number of WBC cells in CSF was significantly higher in patients with positive versus negative FCM with a median value of 12 cells/ul (IQR: 3.5;40) versus 1.0 cells/ul (IQR: 0.0;3.0) (p=0.0120). Univariate and multivariate analyses, using logistic models, showed that abnormal LDH (OR 3.98, 95%CI: 1-15.92)(p=0.05) and number of WBC cells in CSF ≥5 (OR 4.57, 95%CI:1.37-15.33)(p=0.014) were the only predictive factors of a positive test performed by FCM. From date of diagnosis, overall median follow up of survivors was 14 months (IQR:8-22). We observed 39 (30%) systemic progressions, 6 (5%) CNS progressions (in 5 cases an isolated CNS progression whereas 1 pts experienced a CNS along with systemic progression). Thirty-two (25%) patients died and causes of deaths were as follows: 27 progressive disease, 1 infection, 1 treatment related toxicity, 1 hepatitis, 2 unknown. PFS at 1 year was 71% (95%CI:62-78) in the whole group of patients. The progression risk was significantly higher in patients both FCM+/CC+ compared with patients both FCM-/CC- (1-yr PFS 43% vs 74%) (HR 3.8 95%CI:1.6-9.0) (p=0.003). An higher but not significant risk of progression was found in pts discordant (FCM+/CC-) with respect to patients both FCM-/CC- (1-yr PFS 65% vs 74%) (HR 1.61, 95%CI:0.63-4.11) (p=0.315). In the univariate and multivariate analyses performed with Cox models, we found that the presence of ECOG PS≥2 (HR 2.14, 95%CI: 1.14-4)(p=0.018) and level of protein in CSF >40/ul (HR 1.83 95%CI: 1.01-3.29)(p=0.045) were prognostic factor of PFS. Conclusion:FCM assessment of CSF increase the rate of positivity of occult LD compare with CC but it's clinical relevance is still to be clearly defined. Our preliminary data suggest that patients both FCM+/CC+ have an higher risk of progression compared with those both negative, whereas discordant cases may have an intermediate prognosis. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Reactivation of latent bovine herpesvirus type 5 in cattle with polioencephalomalacia induced by ammonium sulphate

In the state Mato Grosso do Sul, Brazil, outbreaks of meningoencephalitis by BoHV-5 and polioencephalomalacia (PEM) display similar epidemiological features, suggesting that meningoencephalitis may be associated with reactivation of a latent BoHV-5 infection, during the development of PEM. To test this hypothesis, four 7-8 months old steers negative for BoHV-5 antibodies were inoculated intranasally with BoHV-5 and received amprolium from day 35 to day 105 after inoculation. Because PEM was not produced during this period, ammonium sulphate was given from day 114 to day 180 after inoculation. Two uninfected control steers received amprolium and ammonium sulphate for the same periods. All inoculated cattle developed antibodies against BoHV-5 after inoculation and the virus was isolated from nasal swabs, indicating that they were infected. Two inoculated steers had clinical signs of PEM after 118 and 146 days after virus inoculation. One was euthanized after a clinical manifestation period of seven days and had severe lesions of PEM and meningoencephalitis. BoHV-5 was isolated from the central nervous system of this animal. The other animal recovered but continued to manifest chronic signs of PEM and was euthanatized. On histological examination, the cerebral cortex, caudate nucleus and thalamus had multifocal areas of malacia and mild meningoencephalitis of the cortex. BoHV-5 was not isolated from the brain. One uninfected control steer had signs of neurological disease on day 158 and had lesions of PEM without meningoencephalitis at necropsy. The simultaneous production of PEM and diffuse meningoencephalitis, with isolation of BoHV-5, in one steer treated with ammonium sulphate, 118 days after BoHV-5 inoculation, suggests that latent BoHV-5 was reactivated in this animal submitted to experimental induction of PEM.

Benign Familial Juvenile Epilepsy in Lagotto Romagnolo Dogs

Background:Idiopathic childhood epilepsies with benign outcomes are well recognized in human medicine, but are not reported in veterinary literature. We recognized such a neurologic syndrome in Lagotto Romagnolo dogs.Animals: Twenty‐five Lagotto Romagnolo puppies from 9 different litters examined because of simple or complex focal seizures and 3 adult Lagotto Romagnolo dogs exhibiting similar clinical signs were used.Methods: Clinical and diagnostic evaluations of affected dogs were conducted, including electromyography, electroencephalography, and other testing.Results: Seizures in puppies began at 5 to 9 weeks of age and usually resolved spontaneously by 8 to 13 weeks. Those with the most severe seizures also had signs of neurologic disease between these seizures, including generalized ataxia and hypermetria. There were no abnormalities in routine laboratory screenings of blood, urine, and cerebrospinal fluid. Electromyography, brainstem auditory‐evoked potentials, and magnetic resonance imaging revealed no specific and consistent abnormalities. Fourteen of 16 (87.5%) affected puppies and 2 of 3 (67%) adult dogs revealed epileptiform activity in the electroencephalogram. Histopathologic examination in 1 puppy and 1 adult dog revealed lesions of Purkinje cell inclusions and vacuolation of their axons restricted to the cerebellum. Pedigree analysis suggests an autosomal recessive mode of inheritance.Conclusions and Clinical Importance: This disorder, with simple or complex focal seizures and cerebellar lesions, represents a newly recognized epileptic syndrome in dogs.

Benign Familial Juvenile Epilepsy in Lagotto Romagnolo Dogs

Idiopathic childhood epilepsies with benign outcomes are well recognized in human medicine, but are not reported in veterinary literature. We recognized such a neurologic syndrome in Lagotto Romagnolo dogs. Twenty-five Lagotto Romagnolo puppies from 9 different litters examined because of simple or complex focal seizures and 3 adult Lagotto Romagnolo dogs exhibiting similar clinical signs were used. Clinical and diagnostic evaluations of affected dogs were conducted, including electromyography, electroencephalography, and other testing. Seizures in puppies began at 5 to 9 weeks of age and usually resolved spontaneously by 8 to 13 weeks. Those with the most severe seizures also had signs of neurologic disease between these seizures, including generalized ataxia and hypermetria. There were no abnormalities in routine laboratory screenings of blood, urine, and cerebrospinal fluid. Electromyography, brainstem auditory-evoked potentials, and magnetic resonance imaging revealed no specific and consistent abnormalities. Fourteen of 16 (87.5%) affected puppies and 2 of 3 (67%) adult dogs revealed epileptiform activity in the electroencephalogram. Histopathologic examination in 1 puppy and 1 adult dog revealed lesions of Purkinje cell inclusions and vacuolation of their axons restricted to the cerebellum. Pedigree analysis suggests an autosomal recessive mode of inheritance. This disorder, with simple or complex focal seizures and cerebellar lesions, represents a newly recognized epileptic syndrome in dogs.

Detection of Autoantibodies to the BTB‐kelch Protein KLHL7 in Cancer Sera

The aim of the study was to search for novel targets of autoantibodies in patients with paraneoplastic neurological syndromes (PNS). PNS are mediated by immune reactions against autoantigen(s) shared by the cancer cells and the nervous system. By serological screening of a rat cerebellum cDNA expression library using anti-Hu-positive sera from three patients with paraneoplastic encephalomyelitis (PEM), we identified an open reading frame encoding an isoform of the BTB-kelch protein KLHL7. Immunohistochemical studies demonstrated that the KLHL7 protein is expressed in the nuclei of neurones, but not in other tissues including various cancers. However, the KLHL7 protein was detected in the nuclei of cancer cell lines. Antibodies to KLHL7 were detected by an immunoprecipitation assay in sera from 12 of 254 (4.7%) patients with various cancers and 2 of 170 blood donors (1.2%). None of 50 sera from patients with multiple sclerosis were positive for KLHL7 antibodies. Sixteen patients with classical PNS and anti-Hu or anti-Yo antibodies were also negative for KLHL7 antibodies. Seven cancer patients with KLHL7 antibodies had various signs of neurological disease that could be related to cancer, whereas the remaining five seropositive cancer patients had no clinical signs of possible PNS. The present results indicate that KLHL7 antibodies are associated with various cancers, and in some patients also with neurological disease. Whether KLHL7 antibodies can be used as paraneoplastic markers for PNS remains to be determined.

Intermittent Exotropia Increasing with Near Fixation: A “Soft” Sign of Neurological Disease

This is a straightforward retrospective review encompassing a 13-year period of patients with intermittent exotropia examined at the Arkansas Children’s Hospital. A total of 94 children <18 years of age were identified with intermittent exotropia. Twenty-eight were excluded from analysis for a variety of reasons, including prior strabismus surgery, inability to obtain reliable strabismus measurements at distance and near, etc. The study group (29 subjects) consisted of children whose measured deviation at near was at least 10 PD greater than their deviation at distance. The control group (37 subjects) had distance deviation greater than or equal to their near deviation. Neurologic status for both groups was assessed by interviewing parents and medical record review, with particular attention to evidence of developmental delay, attention deficit disorder, or seizures. Most patients with these conditions had been previously examined by a pediatric neurologist.

Depletion of natural killer cells does not result in neurologic disease due to Sarcocystis neurona in mice with severe combined immunodeficiency.

Sarcocystis neurona is an apicomplexan parasite that is the primary etiologic agent of equine protozoal myeloencephalitis in horses. Protective immune responses in horses have not been determined, but interferon-gamma (IFN-gamma) is considered critical for protection from neurologic disease in mice. The role of adaptive and innate immune responses in control of parasites was explored by infecting BALB/c, IFN-gamma knockout (GKO), and severe combined immune deficient (SCID) mice with S. neurona (10(4) sporocysts/mouse). Immune competent BALB/c mice eliminated parasites within 30 days, with no sign of neurologic disease, whereas GKO mice developed fulminant neurologic disease. In contrast, SCID mice remained healthy throughout the experimental period despite the persistence of parasite at low levels in some mice. Treatment with anti-IFN-gamma antibody resulted in neurologic disease in infected SCID mice. Although SCID mice lack adaptive immune responses, they have natural killer (NK) cells capable of producing significant quantities of IFN-gamma. Therefore, SCID mice were infected with sporocysts of S. neurona and treated with anti-asialo GM1. Depletion of NK cells, confirmed by flow cytometry, did not result in neurologic disease in SCID mice. These results indicate that IFN-gamma mediates protection from neurologic disease in SCID mice. Protective levels of IFN-gamma may originate from a low number of nondepleted NK cells or from a non-T cell, non-NK cell population.

Cerebral edema in childhood diabetic ketoacidosis: natural history, radiographic findings, and early identification.

Children who develop cerebral edema (CE) during diabetic ketoacidosis (DKA) exhibit definable signs and symptoms of neurological collapse early enough to allow intervention to prevent brain damage. Our objective was to develop a model for early detection of CE in children with DKA. A training sample of 26 occurrences of DKA complicated by severe CE and 69 episodes of uncomplicated DKA was reviewed. Signs of neurological disease were incorporated into a bedside evaluation protocol that was applied to an independent test sample of 17 patients previously reported to have developed symptomatic CE during treatment for DKA. Head computed tomograms and their reports were reviewed. The protocol allowed 92% sensitivity and 96% specificity for the recognition of CE sufficiently early for intervention. The diagnostic criteria were fulfilled in two temporal patterns, defining early- and late-onset CE. Although initial computed tomograms were often normal, the findings also included diffuse CE and focal brain injury, the latter only in patients with an early onset of abnormal neurological signs. CE may occur in the absence of acute changes on head computed tomograms. Early detection of CE at the bedside using an evidence-based protocol permits intervention in time to prevent permanent brain damage.

Bovine herpesvirus type 5 (BHV-5) in a calf with rabies

The brain of an one year old male calf which died with signs of neurological disease was submitted to the laboratory for rabies diagnosis. Microscopical findings included moderate mielitis, mild meningoencephalitis with perivascular cell cuffing and Negri inclusion bodies in Purkinje cells of the cerebellum. Rabies virus infection was further confirmed by the direct fluorescent antibody test as well as by mouse inoculation. In addition, a herpesvirus was isolated from brain tissues. The isolate was antigenic and genetically characterized as bovine herpesvirus type 5 (BHV-5). It was not possible to determine whether BHV-5 played an active role in the outcome of the infection, since, the virus might have been present in a latent form in neural tissues. This is the first report of a mixed rabies/ BHV-5 infection in calves.

Immunoconversion against Sarcocystis neurona in normal and dexamethasone-treated horses challenged with S. neurona sporocysts

Equine protozoal myeloencephalitis is a common neurologic disease of horses in the Americas usually caused by Sarcocystis neurona. To date, the disease has not been induced in horses using characterized sporocysts from Didelphis virginiana, the definitive host. S. neurona sporocysts from 15 naturally infected opossums were fed to horses seronegative for antibodies against S. neurona. Eight horses were given 5×10 5 sporocysts daily for 7 days. Horses were examined for abnormal clinical signs, and blood and cerebrospinal fluid were harvested at intervals for 90 days after the first day of challenge and analyzed both qualitatively (western blot) and quantitatively (anti-17 kDa) for anti- S. neurona IgG. Four of the challenged horses were given dexamethasone (0.1 mg/kg orally once daily) for the duration of the experiment. All challenged horses immunoconverted against S. neurona in blood within 32 days of challenge and in CSF within 61 days. There was a trend ( P=0.057) for horses given dexamethasone to immunoconvert earlier than horses that were not immunosuppressed. Anti-17 kDa was detected in the CSF of all challenged horses by day 61. This response was statistically greater at day 32 in horses given dexamethasone. Control horses remained seronegative throughout the period in which all challenged horses converted. One control horse immunoconverted in blood at day 75 and in CSF at day 89. Signs of neurologic disease were mild to equivocal in challenged horses. Horses given dexamethasone had more severe signs of limb weakness than did horses not given dexamethasone; however, we could not determine whether these signs were due to spinal cord disease or to effects of systemic illness. At necropsy, mild–moderate multifocal gliosis and neurophagia were found histologically in the spinal cords of 7/8 challenged horses. No organisms were seen either in routinely processed sections or by immunohistochemistry. Although neurologic disease comparable to naturally occurring equine protozoal myeloencephalitis (EPM) was not produced, we had clear evidence of an immune response to challenge both systemically and in the CNS. Broad immunosuppression with dexamethasone did not increase the severity of histologic changes in the CNS of challenged horses. Future work must focus on defining the factors that govern progression of inapparent S. neurona infection to EPM.

Ultrastructural Studies of Nipah Virus, A Newly Emergent Paramyxovirus, Using Thin Section, Negative Stain, Immunogold, and in Situ Hybridization Electron Microscopy

Abstract An increase in cases of acute febrile encephalitis occurred in Western Malaysia between September 1998 and May 1999, and a similar illness was reported in Singapore in March 1999. Most cases occurred in males who had been exposed to pigs, or among abattoir workers, and at least 100 deaths were reported. The illness was characterized by fever and headache, followed by drowsiness and disorientation; patients with severe cases developed seizures and coma within 24 to 48 hours. Concurrently, there were also illnesses and deaths among pigs in the same region, although the symptoms predominantly involved the respiratory system, and only a few pigs had signs of neurologic disease. From a cerebral spinal fluid specimen from a human patient, Dr. Chua and colleagues were successful in isolating a virus that was morphologically identified as belonging to the family Paramyxoviridae, and is now known as Nipah virus.

A neurological syndrome in a free-living population of possums (Trichosurus vulpecula)

Aims. To determine the clinical and pathological features of a neurological disease syndrome in a free-living possum population in New Zealand and to compare this syndrome with wobbly possum disease. Methods. An outbreak of a neurological disease in possums in the Rotorua district was investigated in 1994. A variety of tissues was collected and investigated microbiologically and histopathologically. Tissues stored from clinically affected possums were homogenised, clarified and inoculated into healthy possums by the intra-peritoneal route. The clinical signs and histopathological lesions in naturally-infected and in experimentally-inoculated possums were assessed and compared with those of possums affected with wobbly possum disease. Results. Histopathological investigation of three of the naturally-affected possums revealed non-suppurative encephalitis with perivascular cuffing, diffuse non-suppurative meningitis and focal non-suppurative myocarditis.These lesions were suggestive of a viral infection. No pathogenic bacteria were recovered and no viruses were isolated in tissue culture. A neurological disease, indistinguishable from wobbly possum disease, was reproduced in five out of the eight experimentally-inoculated possums. In two experimental cases the clinical signs were very mild and, in most cases of the natural and experimental disease, histopathological lesions in the central nervous system were mild in comparison with wobbly possum disease. Possums which did not develop clinical signs of neurological disease or have lesions in the central nervous system did have infiltrations of mononuclear inflammatory cells in the liver and kidney. Conclusions. This neurological disease, reported for the first time in a free-living population, closely resembles and maybe the same as wobbly possum disease. The milder nature of this disease could suggest there maybe more than one strain of the aetiological agent.

Seizure detection of newborn EEG using a model-based approach.

Seizures are often the first sign of neurological disease or dysfunction in the newborn. However, their clinical manifestation is often subtle, which tends to hinder their diagnosis at the earliest possible time. This represents an undesirable situation since the failure to quickly and accurately diagnose seizure can lead to longer-term brain injury or even death. In this paper we consider the problem of automatic seizure detection in the neonate based on electroencephalogram (EEG) data. We propose a new approach based on a model for the generation of the EEG, which is derived from the histology and biophysics of a localized portion of the brain. We show that by using this approach, good detection performance of electrographic seizure is possible. The model for seizure is first presented along with an estimator for the model parameters. Then we present a seizure-detection scheme based on the model parameter estimates. This scheme is compared with the quadratic detection filter (QDF), and is shown to give superior performance over the latter. This is due to the ability of the model-based detector to account for the variability (nonstationarity) of the EEG by adjusting its parameters appropriately.