Central Nervous Signs Research Articles

The Spontaneous Incidence of Neurological Clinical Signs in Preclinical Species Using Cage-side Observations or High-definition Video Monitoring: A Retrospective Analysis.

When conducting toxicology studies, the interpretation of drug-related neurological clinical signs such as convulsions, myoclonus/myoclonic jerks, tremors, ataxia, and salivation requires an understanding of the spontaneous incidence of those observations in commonly used laboratory animal species. The spontaneous incidence of central nervous system clinical signs in control animals from a single facility using cage-side observations or high definition video monitoring was retrospectively analyzed. Spontaneous convulsions were observed at low incidence in Beagle dogs and Sprague-Dawley rats but were not identified in cynomolgus monkeys and Göttingen minipigs. Spontaneous myoclonic jerks and muscle twitches were observed at low incidence in Beagle dogs, cynomolgus monkeys, and Sprague-Dawley rats but were not seen in Göttingen minipigs. Spontaneous ataxia/incoordination was identified in all species and generally with a higher incidence when using video monitoring. Salivation and tremors were the two most frequent spontaneous clinical signs and both were observed in all species. Data from the current study unveil potential limitations when using control data obtained from a single study for toxicology interpretation related to low incidence neurological clinical signs while providing historical control data from Beagle dogs, cynomolgus monkeys, Sprague-Dawley rats, and Göttingen minipigs.

Challenges of transsphenoidal pituitary surgery in severe brachycephalic dogs.

Transsphenoidal hypophysectomy is the standard surgical technique for the excision of pituitary neoplasms. Anatomy may be more obscured in brachycephalic skull types due to the crowding of soft tissue and osseous structures. We describe the unique challenges to approach the sphenoid bone and localize the correct burr hole site in severe brachycephalic dogs. A single institution retrospective case series of brachycephalic dogs with pituitary-dependent hypercortisolism (PDH). Preoperative computed tomography enabled 3D-, and cross-sectional reconstruction to plan and dry-practice the position of the ideal burr hole in relation to the sella turcica, pterygoid hamular processes, and hard palate. Rostral burring of the caudal hard palate obscuring the direct sphenoid approach necessitated adaptations to the original transsphenoidal hypophysectomy procedure. Postoperative outcomes and complications with respect to those seen in mesocephalic dogs are described. Ten brachycephalic dogs including French Bulldogs (n = 9) and a single Dogue de Bordeaux were included. All dogs were diagnosed with PDH and had preoperative advanced imaging performed on the skull. All but one dog had an enlarged pituitary gland, with a median pituitary/brain value of 0.5 (range 0.21-0.9). A total of 11 transsphenoidal hypophysectomy procedures were performed in these 10 dogs. Rostral extension of the soft palate incision into the hard palate was performed to access the burr hole site on the sphenoid bone. Major complications included aspiration pneumonia (n = 1), severe gastroesophageal reflux (n = 1), and central nervous signs (=1). All dogs survived until discharge, with a median time to follow-up of 618 days (range 79-1,669 days). Seven dogs experienced long-term remission of PDH. Brachycephalic dogs undergoing transsphenoid al hypophysectomy benefit from meticulous presurgical planning and extension of the approach into the caudal hard palate. Advanced surgical skills can render a good outcome in a technically challenging environment.

Tissue Distribution of Parrot Bornavirus 4 (PaBV-4) in Experimentally Infected Young and Adult Cockatiels (Nymphicus hollandicus).

Proventricular dilatation disease (PDD) caused by parrot bornavirus (PaBV) infection is an often-fatal disease known to infect Psittaciformes. The impact of age at the time of PaBV infection on organ lesions and tissue distribution of virus antigen and RNA remains largely unclear. For this purpose, tissue sections of 11 cockatiels intravenously infected with PaBV-4 as adults or juveniles, respectively, were examined via histology, immunohistochemistry applying a phosphoprotein (P) antibody directed against the bornaviral phosphoprotein and in situ hybridisation to detect viral RNA in tissues. In both groups of adult- and juvenile-infected cockatiels, widespread tissue distribution of bornaviral antigen and RNA as well as histologic inflammatory lesions were demonstrated. The latter appeared more severe in the central nervous system in adults and in the proventriculus of juveniles, respectively. During the study, central nervous symptoms and signs of gastrointestinal affection were only demonstrated in adult birds. Our findings indicate a great role of the age at the time of infection in the development of histopathological lesions and clinical signs, and thus provide a better understanding of the pathogenesis, possible virus transmission routes, and the development of carrier birds posing a risk to psittacine collections.

Mycoplasma hyorhinis as a possible cause of fibrinopurulent meningitis in pigs? - a case series

BackgroundMycoplasma hyorhinis is an invader of the upper respiratory tract in swine that is considered to have ubiquitous distribution. It is mainly known for causing polyserositis and polyarthritis in weaned piglets, even though the mechanisms of systemic spread are not fully understood. Mycoplasma hyorhinis has also been associated with other diseases in pigs such as pneumonia or otitis media, but so far has not been known to cause central nervous disorders. This case series reports the isolation of Mycoplasma hyorhinis from cerebrospinal fluid and/ or meningeal swabs from piglets originating from four different piglet producing farms in Austria.Case presentationOn farm 1, coughing, stiff movement and central nervous signs occurred in nursery piglets. Mycoplasma hyorhinis was the only pathogen isolated from meningeal swabs from two piglets showing central nervous signs. Fibrinopurulent leptomeningitis was only observed in one piglet. Only one of two nursery piglets from farm 2 showed mild central nervous signs but no histologic lesions; Mycoplasma hyorhinis was isolated from cerebrospinal fluid of the piglet with neurologic signs. Mycoplasma hyorhinis was isolated from cerebrospinal fluid of all three investigated piglets from farm 3, all of which showed central nervous signs and purulent leptomeningitis. Further, Streptococcus suis was isolated from the cerebrospinal fluid of one piglet. Fibrinopurulent leptomeningitis was detected in two piglets from farm 4 that had died overnight without showing any clinical signs and Mycoplasma hyorhinis was isolated from meningeal swabs from both piglets.ConclusionWhile causality has yet to be proven by experimental infection and in situ detection of the pathogen in histologic sections, the findings of this study and the absence of other pathogens suggest Mycoplasma hyorhinis as a potential causative agent of meningitis in swine.

Keracunan coklat pada anjing: manajemen terapi dan pencegahan

Chocolate poisoning has long been recognized as a common cause mostly in dogs, although many species are susceptible. Contributing factors include indiscriminate eating habits and readily available sources of chocolate. In general, the poisoning resulted from a lack of public knowledge of the health hazard to dogs that may be imposed by these products.Chocolate is derived from the seeds of the plant Theobroma cacao, and the main toxic components are the methylxanthine alkaloids theobromine and caffeine, causing gastrointestinal, cardiovascular and central nervous signs. Diagnosis is based on history of exposure, along with clinical signs. Amphetamine or cocaine toxicosis, and ingestion of antihistamines, antidepressants, or other CNS stimulants should be considered in the differential diagnosis. Stabilization of symptomatic animals is a priority in treating chocolate toxicosis. Although there is no specific antidote, supportive management includes induction of vomiting and administration of activated charcoal, oxygen, and intravenous fluids. Preventing exposure is the key to reducing the incidence of these poisoning episodes. Therefore, it is important to increase the knowledge of dogs owners with regard to foodstuffs that must not be fed to dogs and should be stored outside their reach.

JEPM July 2019 – Abstracts

Background: Lead intoxication is common in companion birds and frequently associated clinical signs include weakness, regurgitation, and central nervous system signs including seizures and tremors. Motor neuropathies and conduction disturbances are more commonly described in humans with lead intoxication, but are uncommon sequelae in psittacine birds. Case Description: Three pet psittacine birds were presented for acute-onset of distal pelvic limb abnormalities. Clinical Findings: An adult, female peach-faced lovebird (Agapornis roseicollis) was presented with acute, bilateral, distal pelvic limb paralysis and an adult, male peach-faced lovebird was presented with an acute inability to extend the digits of the feet bilaterally. An adult blue-streaked lorikeet (Eos reticulata) was presented for acute onset, bilateral pelvic limb weakness, and inability to rise from the bottom of the cage. All three birds had increased blood lead levels (30–110 μg/dL), but none exhibited overt central nervous, gastrointestinal, or other common clinical signs consistent with lead intoxication in birds. A potential source of lead could not be identified in two of the three cases. Conclusion and Case Relevance: Despite achieving persistent reduction of blood lead levels following parenteral chelation therapy using calcium disodium EDTA, all three birds had continued neurological deficits in both pelvic limbs. Birds were considered to maintain a good quality of life after husbandry changes were implemented to assist in ambulation. Lead intoxication should be considered a differential for acute-onset paralysis of the distal pelvic limbs in psittacine birds.

Current Approaches to the Treatment of Hunter Syndrome

Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X-linked hereditary disorder associated with a deficiency of iduronate2-sulfatase (IDS). IDS deficiency provokes the accumulation of dermatan sulfate and heparan sulfate in different tissues. Clinical manifestations of MPS II are heterogeneous and involve different organs. Two phenotypes are distinguished: attenuated or severe; classification is based on central nervous system impairment signs. The review provides data on the current treatments opportunities for Hunter syndrome and perspectives for development of new therapeutic approaches. Current treatment includes intravenous enzyme replacement therapy (ERT), hematopoietic stem cell transplantation, and symptomatic treatment. Intravenous enzyme replacement therapy does not promote the enzyme to penetrate the blood-brain barrier which leads to the treatment failure for neurological signs and symptoms; hematopoietic stem cell transplantation has high risk of post-transplantation complications but can improve some neurological problems. Intrathecal ERT, substrate reduction, pharmacological chaperones, and gene therapy are currently under investigation as therapies for severe form of MPS II. Development of new approaches to treatment of Hunter syndrome and other hereditary diseases is extremely vital.

Cognitive Function, APOE Gene Polymorphisms, and Thyroid Status Associations in Postmenopausal Women in Poland

Background: The objective of the study was to analyze a potential association between cognitive functions and thyroid status in postmenopausal women with different polymorphisms of the apolipoprotein E gene (APOE). Methods: The examined population included 402 postmenopausal women from south-eastern Poland. The evaluation of cognitive functions was made with the use of the diagnostic Central Nervous System-Vital Signs equipment (Polish version). Multiplex polymerase chain reactions were performed to assess APOE polymorphisms. The thyroid hormone tests were assessed by an accredited laboratory. Results and Conclusion: Lower results of cognitive functions were associated with the presence of the ε4 APOE allele in postmenopausal women. The ε4 APOE polymorphism was associated with a higher concentration of thyroid-stimulating hormone and lower concentrations of free triiodothyronine and total triiodothyronine.

An Outbreak of Pestivirus Infection in Sheep in West Kordofan, Sudan

During AprilMay 2010 an outbreak of a disease with obvious nervous and respiratory signs in sheep was reported in west Kordofan State in western Sudan. Four flocks at four different locations in the State were investigated. The deaths by the disease versus the total number of animals in the different areas were 18/150, 1/200, 3/280 and 17/300. The main clinical symptoms observed in adults and young lambs were central nervous signs and respiratory signs; most lambs were weak and emaciated with rough coats. Sera were collected from 11, 18, 19 and 4 of animals in the four Original Research Article Ali et al.; BMRJ, 8(4): 540-545, 2015; Article no.BMRJ.2015.146 541 flocks, respectively. Bacteriological examination on tissue samples did not reveal any positive results. Using competitive ELISA, antibodies against pestivirus were detected in 10/11, 7/18, 7/19 and 1/4, respectively of examined sheep sera in the different locations. RT/PCR using pestvirus specific primers to examine the lung and sera samples showed positive results for one lung and 17 sera samples, and sequence data indicated that the causative agent was Bovine viral diarrhea virus-1 (BVDV-1). This is the first report of BVDV-1 outbreak in sheep in Sudan.

A novel inactivated gE/gI deleted pseudorabies virus (PRV) vaccine completely protects pigs from an emerged variant PRV challenge

A highly virulent and antigenic variant of pseudorabies virus (PRV) broke out in China at the end of 2011 and caused great economic loss in the pig industry. In this study, an infectious bacterial artificial chromosome (BAC) clone containing the full-length genome of the emerged variant PRV ZJ01 strain was generated. The BAC-derived viruses, vZJ01-GFPΔgE/gI (gE/gI deleted strain, and exhibiting green autofluorescence), vZJ01ΔgE/gI (gE/gI deleted strain), and vZJ01gE/gI-R (gE/gI revertant strain), showed similar in vitro growth to their parent strain. In pigs, inactivated vZJ01ΔgE/gI vaccine generated significantly high levels of neutralizing antibodies against ZJ01 compared with Bartha-K61 live vaccine (p<0.05). After fatal ZJ01 challenge, all five animals in the inactivated vZJ01ΔgE/gI vaccine group survived without exhibiting any clinical sings, but two of five animals exhibited central nervous signs in the Bartha-K61 group. Meanwhile, all the non-vaccinated control animals died at 7 days post-challenge. This indicates that the inactivated vZJ01ΔgE/gI vaccine is a promising vaccine candidate for controlling the variant strains of PRV now circulating in China.

Effects of Omega-3 Fatty Acid Supplementation on Neurocognitive Functioning and Mood in Deployed U.S. Soldiers: A Pilot Study

Omega-3 fatty acids (FAs) may have neuroprotective properties for psychological health and cognition. The objective of this study was to evaluate the effectiveness of omega-3 FAs (eicosapentaenoic + docosahexaenoic; Harris-Schacky [HS]-Omega-3 Index) on neuropsychological functioning among U.S. Soldiers deployed to Iraq. This randomized, double-blind, placebo-controlled trial included Soldiers between the ages of 18 and 55 years who were randomly assigned to either the active treatment group (n = 44) or placebo group (n = 34). Active treatment was 2.5 g per day of eicosapentaenoic + docosahexaenoic (Lovaza; GlaxoSmithKline, Research Triangle Park, North Carolina). The placebo was corn oil ethyl esters. HS-Omega-3 Index, a neurocognitive battery (Central Nervous System-Vital Signs, Morrisville, North Carolina), and psychological health scales were assessed at baseline and after 60 days of treatment. Although the results revealed that omega-3 FAs significantly increased the HS-Omega-3 Index (p = 0.001), there were no significant effects on indices psychological health and neurocognitive functioning by treatment group. Nevertheless, there was a significant inverse correlation between the changes in the HS-Omega-3 Index and daytime sleepiness (r = 0.30, p = 0.009). Short-term treatment with 2.5 g of omega-3 FAs did not alter measures of neurocognition or psychological health, but there was evidence of a relationship between omega-3 levels and daytime sleepiness.

Chapter 30 - Neurologic aspects of influenza viruses

Although influenza A and B viruses are primarily known as respiratory viruses and mainly infected only the upper respiratory tract in humans, patients with influenza often develop signs and symptoms that are not due to the respiratory system. Frequently individuals with influenza develop headaches, meningismus, and even seizures in addition to their typical respiratory symptoms. In the past decades, influenza viruses have also been associated with serious non-respiratory signs. The famous 1918 strain of influenza was associated with von Economo's encephalitis lethargica and postencephalitic parkinsonism. In the 1960s influenza virus infections in children were associated with Reye's syndrome characterized often by fatty non-inflammatory hepatic disease and an encephalopathy with marked non-inflammatory cerebral edema. Intermittently children with influenza develop focal myalgia and myositis. Guillain–Barré syndrome was epidemiologically associated with the 1978 killed influenza vaccine but not subsequent vaccines. Although occasional children with influenza have developed encephalopathy, from 2000 through 2004 there was an increase in the number of serious cases of acute necrotizing encephalopathy accompanying infection with the influenza A 2009 strain. The current H5N1 strain of bird influenza occasionally infects humans with a high mortality rate and some appear to have central nervous signs. This chapter explores what is known about these influenza neurologic associations.

An outbreak of Sarcocystis calchasi encephalitis in multiple psittacine species within an enclosed zoological aviary

A total of 5 psittacine birds in an enclosed zoological exhibit, including 2 princess parrots and 3 cockatoos of 2 different species, developed severe central nervous system clinical signs over a 2-3-month period and died or were euthanized. Histologically, all birds had a lymphoplasmacytic and histiocytic encephalitis with intralesional protozoa consistent with a Sarcocystis species in addition to intramuscular tissue sarcocysts. By immunohistochemical staining, merozoites in brain and tissue cysts in muscle did not react with polyclonal antisera against Sarcocystis falcatula, Sarcocystis neurona, Toxoplasma gondii, and Neospora caninum, or with a monoclonal antibody to S. neurona. Transmission electron microscopy on sarcocyst tissue cyst walls from 2 birds was morphologically consistent with Sarcocystis calchasi. Polymerase chain reaction (PCR) amplification and sequencing of partial 18S ribosomal RNA from muscle tissue cysts and brain schizonts from 3 birds was consistent with a clade containing S. calchasi and Sarcocystis columbae but could not distinguish these closely related Sarcocystis species. However, PCR amplification and sequencing of the internal transcribed spacer 1 RNA segment in the brain from 2 birds and muscle from 2 birds specifically identified the isolates as S. calchasi. The current report documents that multiple psittacine species are susceptible intermediate hosts of S. calchasi, and that infection can cause encephalitis resulting in significant morbidity and mortality in psittacine aviaries.

Isolation and molecular characterisation of a pestivirus from goats in Egypt

Nine fetuses and neonates from sheep and goats in Egypt were screened for pestiviruses using immunohistochemistry (IHC), virus isolation, and reverse transcription-polymerase chain reaction (RT-PCR). Two goat kids with typical border disease (BD) were positive for pestivirus infection by immunohistochemistry (IHC) using polyclonal anti-BDV serum but not when four different monoclonal antibodies (MAbs) were used. On inoculation in MDBK cells, a cytopathic bovine viral diarrhoea virus (BVDV) was isolated from one of the two kids. PCR amplification followed by sequencing of the 5'-UTR region confirmed it as BVDV subtype 1b. Although the circulating virus in Egypt is considered to be BVDV 1a, this report confirms the existence of BVDV 1b in addition to BVDV 1a. To our knowledge, this is the first report of isolation of a pestivirus from goats in Egypt and is probably the second report worldwide of a goat kid showing central nervous signs associated with border disease.

Modulation of the host Th1 immune response in pigeon protozoal encephalitis caused by Sarcocystis calchasi

Pigeon protozoal encephalitis (PPE) is an emerging central-nervous disease of domestic pigeons (Columba livia f. domestica) reported in Germany and the United States. It is caused by the apicomplexan parasite Sarcocystis calchasi which is transmitted by Accipter hawks. In contrast to other members of the Apicomplexa such as Toxoplasma and Plasmodium, the knowledge about the pathophysiology and host manipulation of Sarcocystis is scarce and almost nothing is known about PPE. Here we show by mRNA expression profiling a significant down-modulation of the interleukin (IL)-12/IL-18/interferon (IFN)-γ axis in the brains of experimentally infected pigeons during the schizogonic phase of disease. Concomitantly, no cellular immune response was observed in histopathology while immunohistochemistry and nested PCR detected S. calchasi. In contrast, in the late central-nervous phase, IFN-γ and tumor necrosis factor (TNF) α-related cytokines were significantly up-modulated, which correlated with a prominent MHC-II protein expression in areas of mononuclear cell infiltration and necrosis. The mononuclear cell fraction was mainly composed of T-lymphocytes, fewer macrophages and B-lymphocytes. Surprisingly, the severity and composition of the immune cell response appears unrelated to the infectious dose, although the severity and onset of the central nervous signs clearly was dose-dependent. We identified no or only very few tissue cysts by immunohistochemistry in pigeons with severe encephalitis of which one pigeon repeatedly remained negative by PCR despite severe lesions. Taken together, these observations may suggest an immune evasion strategy of S. calchasi during the early phase and a delayed-type hypersensitivity reaction as cause of the extensive cerebral lesions during the late neurological phase of disease.

Vascular mineralization in the brain of horses

Vascular mineralization (siderocalcinosis) in the brain of horses has been usually assumed to be an incidental age-related finding with no clinic significance. In the present study, eight 15-32-year-old horses of different breeds with cerebral siderocalcinosis were studied. Four of these horses had acute and severe central nervous system clinical signs of unknown etiology, 2 horses had neurological signs of known cause, and 2 horses did not have neurological signs. Gross examination of the brains in 4 animals revealed symmetrical foci of malacia in the cerebellar white matter. Histologically, moderate to severe mineralization of blood vessels and parenchyma were observed in all 8 horses, occasionally associated with necrosis of the adjacent tissue. Some horses were tested by virus isolation, polymerase chain reaction, immunohistochemistry, and serology to investigate Rabies virus; West Nile virus; Equid herpesvirus 1 and 4; Eastern, Western, Venezuelan, and Saint Louis encephalitis virus; and Sarcocystis neurona infection. These tests were negative in all samples analyzed. Brain cholinesterase activity and heavy metal screening were also unremarkable. The significance of the vascular and parenchymal mineralization in the brains of some of these horses remains undetermined. However, the severity of the lesions observed in the brains of some of the animals in the present study, coupled with the negative results for other common causes of neurological disease in horses, suggests a possible relationship between siderocalcinosis and the clinical signs observed.

Epidemiological and clinical features of human rabies cases in Bali 2008-2010

BackgroundPreviously thought to be rabies free, Bali experienced an outbreak of animal and human rabies cases in November 2008. We describe the epidemiological and clinical data of human rabies cases occurring in the first two years of the outbreak.MethodsWe analysed the patient records of all rabies cases from the Sanglah General Hospital in Denpasar, and district hospitals in Buleleng and Tabanan. A conventional reverse transcriptase polymerase chain reaction was developed to detect the rabies virus genome in saliva, corneal swabs, and ante- and post-mortem cerebrospinal fluid (CSF).ResultsThere were 104 human rabies cases in Bali during November 2008-November 2010. Patients' mean age was 36.6 years (range 3-84 years; SD 20.7), most were male (56.7%), and originated from rural districts. Almost all (92%) cases had a history of dog bite. Only 5.8% had their wounds treated and received an anti-rabies vaccine (ARV) after the bite incident. No patients received rabies immunoglobulin (RIG). The estimated time from dog bite to the onset of signs and symptoms was 110.4 days (range 12-720 days; SD 118.2). The mean length of medical care until death was 21.8 hours (range 1-220 hours; SD 32.6). Less than 50% of patients had prodromal symptoms. The most frequent prodromal symptom was pain or paraesthesia at the bite site (37.6%). The two most common central nervous system infection signs were agitation (89.2%) and confusion (83.3%). Signs of autonomic nervous system dysfunction included hydrophobia (93.1%), hypersalivation (88.2%), and dyspnea (74.4%). On admission, 22 of 102 patients (21.6%) showed paralytic manifestations, while the rest (78.4%) showed furious rabies manifestations. The case-fatality rate was 100%. The rabies virus genome was detected in 50 of 101 patients (49.5%) with the highest detection rate from post-mortem CSF samples.ConclusionsRabies is a major public health problem in Bali. Human fatalities occur because of a lack of knowledge regarding rabies risk, the poor management of dog bites, and the limited availability of RIG. Increasing public awareness of dog bite management, increasing the availability of ARV and RIG, and implementing an island-wide dog vaccination campaign will help prevent human rabies cases.

Disseminated Toxoplasmosis in Black-Footed Penguins (Spheniscus demersus)

Three 1- to 3-mo-old black-footed penguins (Spheniscus Demersus) died within 24 hr of showing central nervous signs such as ataxia. The birds were housed in a baby penguin crèche. At necropsy, peritonitis, pneumonia, hepatomegaly, splenomegaly, and renomegaly were evident. Histologically, the liver, lung, brain, and small intestine contained numerous tachyzoites and a few cysts of Toxoplasma. Immunohistochemistry identified the protozoal parasites as Toxoplasma gondii. Ultrastructurally, this was confirmed by the presence of many tachyzoites of T. gondii in the liver and lungs.

Fatal equine meningoencephalitis in the United Kingdom caused by the panagrolaimid nematodeHalicephalobus gingivalis: Case report and review of the literature

A fatal case of eosinophilic and granulomatous meningoencephalitis caused by the free-living panagrolaimid nematode Halicephalobus gingivalis is reported in a 10-year-old Welsh gelding in the United Kingdom. Clinical examination first revealed behavioural abnormalities which rapidly progressed to severe ataxia, reduced mentation status and cranial nerve signs. Despite symptomatic treatment no amelioration of neurological signs was achieved and the horse was subjected to euthanasia. A complete post mortem examination revealed eosinophilic and granulomatous meningoencephalitis mainly affecting the cerebellum and brain stem with intralesional adult nematodes, larvae and eggs. There was also eosinophilic meningitis of the cervical spinal cord. The intralesional nematodes were morphologically consistent with the panagrolaimid nematode H. gingivalis. Although infection by this facultative neurotropic parasite is extremely rare, it needs to be considered in the differential diagnosis of central nervous signs in horses and, in particular, other equine helminthic infection of the central nervous system. This fatal case is unusual since lesions were locally very extensive and the nematodes did not colonise haematogenously to other organs as seen often in equine halicephalobosis. As the taxonomy of H. gingivalis has changed and some recent reports in the literature still refer to this species as Micronema deletrix or Halicephalobus deletrix, we here provide a short update of the species and some insights on the order Tylenchida, which contains free-living nematodes with parasitic tendencies.

Diagnosis and treatment of urea cycle disorders

Urea cycle disorders (UCDs) comprise a group of inherited defects of metabolism affecting the detoxification of excess nitrogen and, hereby, leading to hyperammonemia. The urea cycle consists of six consecutive enzymatic steps and is located both in the mitochondria and cytosol of periportal hepatocytes. In addition, two transporters are required for the urea cycle function. Besides the detoxification of excess nitrogen, the endogenous synthesis of the amino acid arginine is the second role of the urea cycle. The clinical presentation of UCDs comprises a continuum ranging from early onset hyperammonemic decompensation in severe defects to late onset presentation in less severe affected patients at any age. Since ammonia is primarily toxic to the central nervous system, signs and symptoms of UCDs are mainly neurological but, unfortunately, highly unspecific. Therefore, it can be challenging to clinically diagnose patients suffering from UCDs. If a UCD is suspected, ammonia should be measured immediately. To confirm the diagnosis, a variety of biochemical, enzymatic and genetic tools exist. Most UCD patients need a strict treatment protocol consisting of dietary protein restriction, nitrogen scavenger drugs, and vitamin and amino acid supplementations. Treatment must be followed lifelong unless liver transplantation is performed. Patients with UCDs are still affected by a poor outcome quoad vitam et sanitam. To improve both survival rates as well as the quality of life in surviving patients will largely depend on an increased awareness of all medical professionals towards this group of inherited metabolic defects.