Progressive Neurological Signs Research Articles

Asystole associated with cerebrospinal fluid collection in a 3‐month‐old foal under general anaesthesia

SummaryA 3‐month‐old colt foal presented to the Philip Leverhulme Equine Hospital for investigation of progressive neurological signs. Diagnostic investigation included cerebrospinal fluid collection, which was performed under general anaesthesia. During this procedure, severe bradycardia which progressed to asystole occurred. Initial resuscitation was successful; however, the foal had clinical signs consistent with cerebral hypoxia post‐resuscitation and was euthanased the following day due to deterioration of neurological function. Asystole was presumed due to a Cushing‐type reflex as a result of changes in intracranial pressure during the sampling procedure.

Neuronal Ceroid Lipofuscinosis in a Domestic Cat Associated with a DNA Sequence Variant That Creates a Premature Stop Codon in CLN6.

A neutered male domestic medium-haired cat presented at a veterinary neurology clinic at 20 months of age due to progressive neurological signs that included visual impairment, focal myoclonus, and frequent severe generalized seizures that were refractory to treatment with phenobarbital. Magnetic resonance imaging revealed diffuse global brain atrophy. Due to the severity and frequency of its seizures, the cat was euthanized at 22 months of age. Microscopic examination of the cerebellum, cerebral cortex and brainstem revealed pronounced intracellular accumulations of autofluorescent storage material and inflammation in all 3 brain regions. Ultrastructural examination of the storage material indicated that it consisted almost completely of tightly-packed membrane-like material. The clinical signs and neuropathology strongly suggested that the cat suffered from a form of neuronal ceroid lipofuscinosis (NCL). Whole exome sequence analysis was performed on genomic DNA from the affected cat. Comparison of the sequence data to whole exome sequence data from 39 unaffected cats and whole genome sequence data from an additional 195 unaffected cats revealed a homozygous variant in CLN6 that was unique to the affected cat. This variant was predicted to cause a stop gain in the transcript due to a guanine to adenine transition (ENSFCAT00000025909:c.668G > A; XM_003987007.5:c.668G > A) and was the sole loss of function variant detected. CLN6 variants in other species, including humans, dogs, and sheep, are associated with the CLN6 form of NCL. Based on the affected cat’s clinical signs, neuropathology and molecular genetic analysis, we conclude that the cat’s disorder resulted from the loss of function of CLN6. This study is only the second to identify the molecular genetic basis of a feline NCL. Other cats exhibiting similar signs can now be screened for the CLN6 variant. This could lead to establishment of a feline model of CLN6 disease that could be used in therapeutic intervention studies.

Clinical and MRI findings in two unrelated cats with globoid cell leucodystrophy

Two unrelated male cats, both five months old, were referred for progressive neurological signs characterised by intentional tremors, paraplegia with absence of nociception in the pelvic limbs, weakness, dysmetria with reduced flexor reflex in the thoracic limbs, and bilaterally reduced menace response. MRI, performed by a 0.25 T Esaote Vet Grande, showed diffuse and irregular intramedullary T2 weighted hyperintensity between T3 and L3; these lesions were isointense on T1 weighted images without contrast uptake. In one patient MRI of the brain was obtained and mild cerebellar volume reduction was found. Histological examination of the brain and spinal cord demonstrated myelin loss and perivascular accumulation of periodic acid-Schiff-positive big macrophages. These findings were consistent with globoid cell leucodystrophy, as previously described in cats. Although not specific, in young cats with progressive spinal neurological signs, especially when associated with cerebellar signs, and irregular but diffuse T2 intramedullary hyperintensity and T1 isointensity without contrast uptake, globoid cell leucodystrophy should be suspected.

Listeria monocytogenes meningoencephalomyelitis most likely due to septic spread as a rare cause of neurological disease and fever in an adult horse

A 14-year-old warmblood mare developed progressive neurological signs including ataxia, nystagmus, impaired mental status as well as decreased cranial nerve reflexes, and finally went recumbent. Postmortem examination and histology revealed...

Intracerebral Astrocytoma in a Horse

An 8-year-old Anglo-European gelding with progressive neurological signs was humanely destroyed and submitted for necropsy examination. The right parietal cortex was disrupted by a well-demarcated, intraparenchymal, 1.5cm diameter, tan, homogeneous, dense mass. Microscopical examination was consistent with an astrocytoma, which was confirmed on the basis of strong immunohistochemical labelling for glial fibrillary acidic protein. The neoplastic population lacked immunolabelling for oligodendrocyte transcription factor 2. Labelling for ionized calcium binding adaptor molecule 1 highlighted large numbers of reactive microglia throughout the proliferation and in the adjacent neuroparenchyma. While rare, primary brain tumours should be considered as a differential in horses presenting with progressive neurological signs.

Pediatric Motor Inflammatory Neuropathy: The Role of Antiphospholipid Antibodies

We report the clinical case of a nine-year-old girl who presented with progressive motor neuropathy, revealed via the detection of a higher delay in F-wave recording using digitalized nerve conduction/electromyography. Since the lupus anticoagulant (LAC) positivity, detected using diluted Russell viper venom time (dRVVT), switched to persistent serological anticardiolipin immunoglobulin G (IgG) positivity, a possible non-thrombotic antiphospholipid antibody (aPL)-related clinical manifestation was suspected, and intravenous immunoglobulin treatment (IVIG) was started. The IVIG treatment was well tolerated and the complete resolution of motor impairment was obtained after the third IVIG infusion. Our findings suggest that it could be useful to check for antiphospholipid antibodies in children with a rapid onset of progressive neurological signs in order to provide the beneficial use of IVIG in the treatment of pediatric aPL neurological conditions.

Primary progressive multiple sclerosis presenting under the age of 18 years: Fact or fiction?

Previous cohort studies on paediatric multiple sclerosis (MS) have reported very low frequencies for a primary progressive MS (PPMS) course ranging from 0% to 7%. We identified six patients presenting prior to the age of 18 years and fulfilling the 2017 McDonald Criteria for PPMS. Presentation with progressive neurological symptoms and signs in young people should prompt evaluation for genetic causes such as leukodystrophies, hereditary spastic paraparesis and mitochondrial diseases given the rarity of primary progressive course in paediatric MS. In the absence of an alternative diagnosis, with new therapeutic options becoming available for PPMS, this diagnosis should then be considered.

An exonic insertion in the NAGLU gene causing Mucopolysaccharidosis IIIB in Schipperke dogs

Mucopolysaccharidosis (MPS) IIIB (Sanfilippo syndrome B; OMIM 252920), is a lysosomal storage disease with progressive neurological signs caused by deficient activity of alpha-N-acetylglucosaminidase (NAGLU, EC 3.2.1.50). Herein we report the causative variant in the NAGLU gene in Schipperke dogs and a genotyping survey in the breed. All six exons and adjacent regions of the NAGLU gene were sequenced from six healthy appearing and three affected Schipperkes. DNA fragment length and TaqMan assays were used to genotype privately owned Schipperkes. A single variant was found in exon 6 of MPS IIIB affected Schipperkes: an insertion consisting of a 40–70 bp poly-A and an 11 bp duplication of the exonic region preceding the poly-A (XM_548088.6:c.2110_2111ins[A(40_70);2100_2110]) is predicted to insert a stretch of 13 or more lysines followed by either an in-frame insertion of a repeat of the four amino acids preceding the lysines, or a frameshift. The clinically affected Schipperkes were homozygous for this insertion, and the sequenced healthy dogs were either heterozygous or homozygous for the wild-type allele. From 2003–2019, 3219 Schipperkes were genotyped. Of these, 1.5% were homozygous for this insertion and found to be clinically affected, and 23.6% were heterozygous for the insertion and were clinically healthy, the remaining 74.9% were homozygous for the wild-type and were also clinically healthy. The number of dogs homozygous and heterozygous for the insertion declined rapidly after the initial years of genotyping, documenting the benefit of a DNA screening program in a breed with a small gene pool. In conclusion, a causative NAGLU variant in Schipperke dogs with MPS IIIB was identified and was found at high frequency in the breed. Through genotyping and informed breeding practices, the prevalence of canine MPS IIIB has been drastically reduced in the Schipperke population worldwide.

Abstract P2-20-01: Impact of neratinib on development and progression of central nervous system (CNS) metastases in patients with HER2-positive metastatic breast cancer (MBC): Findings from the NALA, NEfERT-T, and TBCRC 022 trials

Abstract Background: The development of metastatic disease in the CNS presents a considerable challenge in the management of patients with MBC as a result of the lack of evidence-based treatment options currently available. Up to 50% of patients with HER2+ MBC develop CNS metastases. A (non-significant) reduction in the cumulative incidence of CNS recurrences was seen in the randomized phase 3 ExteNET trial of neratinib as extended adjuvant treatment of patients with early-stage HER2+ breast cancer following adjuvant trastuzumab-based therapy (Martin et al. Lancet Oncol 2017). Here we review data from the following three trials of neratinib in the metastatic setting: the Phase 3 NALA trial (ClinicalTrials.gov: NCT01808573; Saura et al. ASCO 2019), the Phase 2 NEfERT-T trial (NCT00915018; Awada et al. JAMA Oncol 2016); and the TBCRC 022 trial (NCT01494662; Freedman et al. J Clin Oncol 2019), which suggest activity for neratinib in patients with MBC and CNS metastases. Methods: Patients in NALA (who had received at least 2 lines of HER2-directed therapy for MBC) were randomized 1:1 to neratinib (N; 240 mg qd po) + capecitabine (C; 750 mg/m2 bid po) or lapatinib (L; 1250 mg qd po) + C (1000 mg/m2 bid po). In the NEfERT-T trial, previously untreated patients with recurrent and/or MBC were randomized 1:1 to N (240 mg qd po) or trastuzumab (T; 4 mg/kg then 2 mg/kg weekly), each combined with paclitaxel (P; 80 mg/m2 on days 1, 8, and 15 every 28 days). In TBCRC 022, patients with measurable, progressive HER2+ brain metastases received N (240 mg qd po) + C (750 mg/m2 qd po). The co-primary endpoints in NALA were centrally assessed progression-free survival (PFS) and overall survival (OS); time to intervention for symptomatic metastatic CNS disease was a secondary endpoint. PFS was the primary endpoint in NEfERT-T; frequency of and time to symptomatic and/or progressive CNS lesions was a secondary endpoint. The primary endpoint in TBCRC 022 was composite CNS objective response rate (ORR), requiring a reduction of ≥50% in the sum of target CNS lesion volumes without progression of non-target lesions, new lesions, escalating steroids, progressive neurologic signs or symptoms, or non-CNS progression. Results: CNS outcomes in NALA, NEfERT-T, and TBCRC 022 are summarized in the Table. In NALA, significantly fewer N+C vs L+C-treated patients required intervention for symptomatic CNS metastases. In NEfERT-T, the frequency of symptomatic or progressive CNS recurrences was significantly reduced and the time to onset of CNS progression significantly delayed in the N+P group vs the T+P group. In TBCRC 022, almost half of L-naive patients had a partial response using composite criteria. Table. Overall/CNS outcomes in NALA, NEfERT-T, and TBCRC 022NALANEfERT-TTBCRC 022N+CL+CN+PT+PL-naive N+CL-treated N+CNo. of patients3073142422373712ORR, %332775781443Composite CNS ORR, %aN/AN/AN/AN/A4933CBR, %45*368885N/AN/APFSHR (p-value)0.76 (0.0059)1.02 (0.89)N/AMedian, months8.8b6.6b12.912.95.53.1OSHR (p-value)0.88 (0.2086)1.05 (0.77)N/AMedian, months24.0b22.2bNENE13.315.1Intervention for CNS disease, overall cumulative incidence, %22.8*29.2N/AN/AN/AN/AProgressive CNS disease, cumulative incidence, %c11.213.910.1**20.2N/AN/A*p<0.05 for N+C vs L+C. **p=0.002 for N+P vs T+P. aDefined as a reduction of ≥50% in the sum of target CNS lesion volumes without progression of non-target lesions, new lesions, escalating steroids, progressive neurologic signs or symptoms, or non-CNS progression. bRestricted mean values. cOverall cumulative index in NALA; 2-year cumulative index in NEfERT-T. CBR = clinical benefit rate; N/A = not applicable. NE = not estimable.Conclusions: Neratinib has demonstrated activity against CNS brain metastasis in the setting of advanced and metastatic breast cancer and may also limit the development of new CNS metastases in the adjuvant setting. A pooled analysis of data from NALA and NEfERT-T, which will enable subgroup analyses to be performed, is underway and will be presented at the meeting. Citation Format: Ahmad H Awada, Adam M Brufsky, Cristina Saura, Rachel A Freedman, Nancy U Lin, Judith Bebchuk, Feng Xu, Sara Hurvitz. Impact of neratinib on development and progression of central nervous system (CNS) metastases in patients with HER2-positive metastatic breast cancer (MBC): Findings from the NALA, NEfERT-T, and TBCRC 022 trials [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-20-01.

Finnish gelsolin amyloidosis causes significant disease burden but does not affect survival: FIN-GAR phase II study

BackgroundHereditary gelsolin (AGel) amyloidosis is an autosomal dominantly inherited systemic amyloidosis that manifests with the characteristic triad of progressive ophthalmological, neurological and dermatological signs and symptoms. The National Finnish Gelsolin Amyloidosis Registry (FIN-GAR) was founded in 2013 to collect clinical data on patients with AGel amyloidosis, including altogether approximately one third of the Finnish patients. We aim to deepen knowledge on the disease burden and life span of the patients using data from the updated FIN-GAR registry. We sent an updated questionnaire concerning the symptoms and signs, symptomatic treatments and subjective perception on disease progression to 240 members of the Finnish Amyloidosis Association (SAMY). We analyzed the lifespan of 478 patients using the relative survival (RS) framework.ResultsThe updated FIN-GAR registry includes 261 patients. Symptoms and signs corresponding to the classical triad of ophthalmological (dry eyes in 93%; corneal lattice amyloidosis in 89%), neurological (numbness, tingling and other paresthesias in 75%; facial paresis in 67%), and dermatological (drooping eyelids in 86%; cutis laxa in 84%) manifestations were highly prevalent. Cardiac arrhythmias were reported by 15% of the patients and 5% had a cardiac pacemaker installed. Proteinuria was reported by 13% and renal failure by 5% of the patients. A total of 65% of the patients had undergone a skin or soft tissue surgery, 26% carpal tunnel surgery and 24% at least unilateral cataract surgery. As regards life span, relative survival estimates exceeded 1 for males and females until the age group of 70–74 years, for which it was 0.96.ConclusionsAGel amyloidosis causes a wide variety of ophthalmological, neurological, cutaneous, and oral symptoms that together with repeated surgeries cause a clinically significant disease burden. Severe renal and cardiac manifestations are rare as compared to other systemic amyloidoses, explaining in part the finding that AGel amyloidosis does not shorten the life span of the patients at least for the first 75 years.

The First Case of Bovine Astrovirus-Associated Encephalitis in the Southern Hemisphere (Uruguay), Uncovers Evidence of Viral Introduction to the Americas From Europe

Astrovirus species members of the Mamastrovirus genus (family Astroviridae) have been increasingly recognized as neuroinvasive pathogens in various mammals, including humans, mink, cattle, sheep, and pigs. While cases of astrovirus-associated encephalitis have been reported in North America, Europe, and Asia, their presence has never been documented in the Southern hemisphere. This paper describes a case of astrovirus-associated encephalitis in cattle in Uruguay that broadens the geographic distribution and genetic diversity of neuroinvasive astroviruses and provides phylogeographic evidence of viral introduction to the Americas from Europe. A 22-month-old Holstein steer from a farm in Colonia Department, Uruguay developed progressive neurological signs over a 3-days period before dying. Histopathological examination of the brain and proximal cervical spinal cord revealed disseminated, moderate to severe lymphocytic, histiocytic, and plasmacytic poliomeningoencephalomyelitis with neuronal necrosis. A Mamastrovirus strain in the CH13/NeuroS1 clade, that we called bovine astrovirus (BoAstV)-Neuro-Uy, was identified by reverse transcriptase PCR followed by nearly complete genome sequencing. Additionally, BoAstV was detected intralesionally in the brain by chromogenic RNA in situ hybridization within neuronal perikarya, axons and dendrites. Phylogenetic analysis of BoAstV-Neuro-Uy revealed a close relationship to neurotropic BoAstVs within the Virginia/Human-Mink-Ovine clade, which contains a growing cadre of neuroinvasive astroviruses. Analyzing the complete coding region of neuroinvasive BoAstVs sequences available in GenBank, we estimated an evolutionary rate of 4.27 × 10-4 (95% HPD 2.19–6.46 × 10-4) nucleotide substitutions/site/year. Phylogeographic analysis suggests that the common viral ancestor circulated in Europe between 1794–1940, and was introduced in Uruguay between 1849–1967, to later spread to North America and Japan.

A mixed breed dog with neuronal ceroid lipofuscinosis is homozygous for a CLN5 nonsense mutation previously identified in Border Collies and Australian Cattle Dogs

The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterized by progressive declines in neurological functions following normal development. The NCLs are distinguished from similar disorders by the accumulation of autofluorescent lysosomal storage bodies in neurons and many other cell types, and are classified as lysosomal storage diseases. At least 13 genes contain pathogenic sequence variants that underlie different forms of NCL. Naturally occurring canine NCLs can serve as models to develop better understanding of the disease pathologies and for preclinical evaluation of therapeutic interventions for these disorders. To date 14 sequence variants in 8 canine orthologs of human NCL genes have been found to cause progressive neurological disorders similar to human NCLs in 12 different dog breeds. A mixed breed dog with parents of uncertain breed background developed progressive neurological signs consistent with NCL starting at approximately 11 to 12 months of age, and when evaluated with magnetic resonance imaging at 21 months of age exhibited diffuse brain atrophy. Due to the severity of neurological decline the dog was euthanized at 23 months of age. Cerebellar and cerebral cortical neurons contained massive accumulations of autofluorescent storage bodies the contents of which had the appearance of tightly packed membranes. A whole genome sequence, generated with DNA from the affected dog contained a homozygous C-to-T transition at position 30,574,637 on chromosome 22 which is reflected in the mature CLN5 transcript (CLN5: c.619C > T) and converts a glutamine codon to a termination codon (p.Gln207Ter). The identical nonsense mutation has been previously associated with NCL in Border Collies, Australian Cattle Dogs, and a German Shepherd-Australian Cattle Dog mix. The current whole genome sequence and a previously generated whole genome sequence for an Australian Cattle Dog with NCL share a rare homozygous haplotype that extends for 87 kb surrounding 22: 30, 574, 637 and includes 21 polymorphic sites. When genotyped at 7 of these polymorphic sites, DNA samples from the German Shepherd-Australian Cattle Dog mix and from 5 Border Collies with NCL that were homozygous for the CLN5: c.619 T allele also shared this homozygous haplotype, suggesting that the NCL in all of these dogs stems from the same founding mutation event that may have predated the establishment of the modern dog breeds. If so, the CLN5 nonsence allele is probably segregating in other, as yet unidentified, breeds. Thus, dogs exhibiting similar NCL-like signs should be screened for this CLN5 nonsense allele regardless of breed.

Long-term survival with stereotactic radiotherapy for imaging-diagnosed pituitary tumors in dogs.

Published studies on the use of stereotactic radiotherapy for dogs with pituitary tumors are limited. This retrospective observational study describes results of stereotactic radiotherapy for 45 dogs with imaging-diagnosed pituitary tumors. All dogs were treated at a single hospital during the period of December 2009-2015. The stereotactic radiotherapy was delivered in one 15 Gray (Gy) fraction or in three 8 Gy fractions. At the time of analysis, 41 dogs were deceased. Four were alive and censored from all survival analyses; one dog received 8 Gy every other day and was removed from protocol analyses. The median overall survival from first treatment was 311 days (95% confidence interval 226-410 days [range 1-2134 days]). Thirty-two dogs received 15 Gy (median overall survival 311 days; 95% confidence interval [range 221-427 days]), and 12 received 24 Gy on three consecutive days (median overall survival 245 days, 95% confidence interval [range 2-626 days]). Twenty-nine dogs had hyperadrenocorticism (median overall survival 245 days), while 16 had nonfunctional masses (median overall survival 626 days). Clinical improvement was reported in 37/45 cases. Presumptive signs of acute adverse effects within 4 months of stereotactic radiotherapy were noted in 10/45, and most had improvement spontaneously or with steroids. Late effects versus tumor progression were not discernable, but posttreatment blindness (2), hypernatremia (2), and progressive neurological signs (31) were reported. There was no statistical difference in median overall survival for different protocols. Patients with nonfunctional masses had longer median overall survival than those with hyperadrenocorticism (P=0.0003). Survival outcomes with stereotactic radiotherapy were shorter than those previously reported with definitive radiation, especially for dogs with hyperadrenocorticism.

Low mood, visual hallucinations, and falls \u2013 heralding the onset of rapidly progressive probable sporadic Creutzfeldt\u2013Jakob disease in a 73-year old: a case report

BackgroundCreutzfeldt–Jakob disease is a rare and rapidly fatal neurodegenerative disease. Since clinicians may see only very few cases during their professional career, it is important to be familiar with the clinical presentation and progression, to perform appropriate investigations, and allow for quick diagnosis.Case presentationA 73-year-old British Caucasian woman presented with acute confusion of 2 weeks’ duration on a background of low mood following a recent bereavement. Her symptoms included behavioral change, visual hallucinations, vertigo, and recent falls. She was mildly confused, with left-sided hyperreflexia, a wide-based gait, and intention tremor in her left upper limb. Initial blood tests, computed tomography, and magnetic resonance imaging of her brain showed no significant abnormality. Following admission, she had rapid cognitive decline and developed florid and progressive neurological signs; a diagnosis of prion disease was suspected. A lumbar puncture was performed; cerebrospinal fluid was positive for 14–3-3 protein, real-time quaking-induced conversion, and raised levels of s-100b proteins were detected. An electroencephalogram showed bilateral periodic triphasic waves on a slow background. The diagnosis of probable Creutzfeldt–Jakob disease was made.ConclusionsThis case report highlights key features in the initial presentation and clinical development of a rare but invariably rapidly progressive and fatal disease. It emphasizes the importance of considering a unifying diagnosis for multifaceted clinical presentations. Although it is very rare, Creutzfeldt–Jakob disease should be considered a diagnosis for a mixed neuropsychiatric presentation, particularly with rapid progressive cognitive decline and development of neurological signs. However, to avoid overlooking early signal change on magnetic resonance imaging, it is important to take diffusion-weighted magnetic resonance imaging for all patients with neuropsychological symptoms. Importantly, early diagnosis also ensures the arrangement of suitable contamination control measures to minimize the risk of infection to health care professionals and other patients.

The impact of ammonia levels and dialysis on outcome in 202 patients with neonatal onset urea cycle disorders.

Neonatal onset hyperammonemia in patients with urea cycle disorders (UCDs) is still associated with high morbidity and mortality. Current protocols consistently recommend emergency medical and dietary management. In case of increasing or persistent hyperammonemia, with continuous or progressive neurological signs, dialysis is performed, mostly as ultima ratio. It is presently unknown whether the currently defined ammonia threshold (e.g., at 500μmol/L) to start dialysis is useful to improve clinical outcome. A systematic review of clinical and biochemical data from published neonatal onset UCD patients was performed to identify factors determining clinical outcome and to investigate in which clinical and biochemical setting dialysis was most effective. A total of 202 patients (118 proximal and 84 distal UCDs) described in 90 case reports or case series were included according to predefined inclusion/exclusion criteria. Median age at onset was three days and mean ammonia that triggered start of dialysis was 1199μmol/L. Seventy-one percent of all patients received any form of dialysis. Total mortality was 25% and only 20% of all patients had a "normal" outcome. In general, patients with higher ammonia levels were more likely to receive dialysis, but this had for most patients no influence on outcome. In conclusion, in severe neonatal onset hyperammonemia, the current practice of dialysis, which effectively clears ammonia, had no impact on outcome. It may be essential for improving outcome to initiate all available treatment options, including dialysis, as early as possible.

Mucopolysaccharidosis IIIB (Sanfilippo syndrome B) in a commercial emu (Dromaius novaehollandiae) flock

ABSTRACTClinicopathological diagnosis of mucopolysaccharidosis type IIIB (MPS IIIB; Sanfilippo syndrome B), an inherited autosomal recessive lysosomal storage disease, as a cause of losses in a commercial emu flock and screening breeders using a mutation-specific DNA test are described. Between 2012 and 2015, ∼5–10 juvenile emus from a few weeks to several months of age developed progressive neurological signs and died while others in the flock remained healthy. Necropsy of two affected siblings revealed multiple sites of haemorrhage, cytoplasmic periodic acid-Schiff and Luxol fast blue-positive inclusions in neurons, and aggregates of foamy macrophages in visceral organs. Affected emus were homozygous for the two-base deletion in the α-N-acetylglucosaminidase gene that causes MPS IIIB in emus. Mutation-specific DNA tests for MPS IIIB in emus were developed. Screening blood samples from 78 breeding emus revealed 14 (18%; 9 males, 4 females, and 1 unknown gender) carriers; an overall 0.09 mutant α-N-acetylglucosaminidase allele frequency. A “test and cull male carriers” programme, in which carrier males are culled but carrier females are retained, was proposed to avoid breeding affected emus together, ultimately eliminating the disease from future broods, and preserving the gene pool with as much breeding stock as possible. Molecular genetic diagnostic tests are simple, precise, and permit screening of all breeders for the mutant allele in any flock and can be used to eliminate MPS IIIB-related emu losses through informed breeding.

A novel astrovirus associated with encephalitis and ganglionitis in domestic sheep.

In June 2013, a 4-year-old Welsh Mountain ewe and in March 2014 a 10-day-old lamb of the same breed and the same flock presented progressive neurological signs including depressed sensorium, tremor, and unusual behaviour. Neuropathological examination of the brain and spinal cord detected non-suppurative polioencephalomyelitis and dorsal root ganglionitis, characteristic of a neurotropic viral agent in both sheep. Metagenomic analysis of different tissue samples from both animals identified a novel Ovine Astrovirus (OvAstV). The presence of viral genome in the central nervous system was confirmed by RT-qPCR. Although the cases presented nine months apart, the identified OvAstV shared nearly identical sequences, differing in only three nucleotide positions across the complete genome. Phylogenetic analysis revealed a close relation of OvAstV to neurotropic bovine astroviruses and an enteric OvAstV. In conclusion, these are the first reported cases of astrovirus infection in domestic sheep that were associated with encephalitis and ganglionitis.

CLINICAL AND MAGNETIC RESONANCE IMAGING FEATURES OF IDIOPATHIC OCULOMOTOR NEUROPATHY IN 14 DOGS.

Ophthalmoplegia/ophthalmoparesis (internal, external, or both) has been reported in dogs secondary to neoplasia affecting the oculomotor nerve and is usually given a poor prognosis. The purpose of this retrospective study was to describe the clinical findings, magnetic resonance imaging (MRI) findings, management, outcome, and follow-up in a group of canine cases with idiopathic oculomotor neuropathy. Inclusion criteria included cases with ophthalmoplegia/ophthalmoparesis (internal, external or both) as sole neuroophthalmologic signs, complete ophthalmic and neurologic examination, head MRI, and a minimum follow-up period of 1 year. Dogs with progressive neurological signs not related to oculomotor neuropathy were excluded. Fourteen cases met the inclusion criteria. All cases were unilaterally affected. Magnetic resonance imaging showed equivocal enlargement of the oculomotor nerve in three cases, mild enlargement in five, and marked enlargement in six. Contrast enhancement was present in 12 cases, being marked in six. When present, the contrast enhancement was focal in eight cases and diffuse in four. The median follow-up time was 25 months. External ophthalmoparesis improved in seven cases, five cases under no treatment and two under systemic corticosteroid therapy. The clinical signs in the other seven cases remained unchanged. Idiopathic oculomotor neuropathy should be included as a differential diagnosis in dogs presenting with unilateral ophthalmoplegia/ophthalmoparesis (internal, external, or both) with the absence of other neurologic and ophthalmic signs, and with the MRI findings restricted to the oculomotor nerve. Idiopathic oculomotor neuropathy has a good prognosis as the clinical signs do not deteriorate and they can improve without treatment.

Rapidly Progressive Encephalopathy: Initial Diagnosis of Creutzfeldt Jakob Disease in an Intensive Care Unit.

Creutzfeldt-Jakob disease (CJD) is a rare, incurable and fatal condition that can only be confirmed through neuropathological investigation, such as brain biopsy or post-mortem study. However, a probable diagnosis can be made using clinical criteria. CJD manifests as rapidly progressive dementia with myoclonus and to a lesser extent visual impairment and cerebellar and pyramidal/extrapyramidal signs. We report the case of a previously independent adult male that met all the clinical criteria. Taken together, the investigation results suggested probable CJD.LEARNING POINTSCreutzfeldt-Jakob disease (CJD) is a rare cause of dementia.The rapidly progressive neurological signs and symptoms suggest the diagnosis.Mortality rates are very high even with surgical treatment in these complex patients.

Gemistocytic astrocytoma in the spinal cord in a dog: a case report

ABSTRACT This paper reports a case of a rare variant of the cervical spinal cord astrocytoma diagnosed in a dog with progressive neurological signs, initially asymmetrical, not ambulatory tetraparesis, segmental reflexes and normal muscle tone in all four limbs and absence of pain upon palpation of the cervical spine. Myelography revealed attenuation of the ventral and dorsal contrast line in the third region of the fifth cervical vertebra. At necropsy intramedullary cylindrical mass that stretched from the third to the sixth cervical vertebra, which replaced all the gray matter of the spinal cord was observed. In the histological study, there was the replacement of the substance by neoplastic cells mantle arranged loosely. The cells were large and slightly rounded. The eosinophilic cytoplasm was well defined, sometimes forming processes interconnecting cells. The nucleus was eccentric, round, oval or kidney-shaped, and the nucleolus was evident. Thus, the microscopic changes observed in the cervical spinal cord were consistent with gemistocytic astrocytoma.