Positioning head tilt observed in two cats with myasthenia gravis.

Case series summary: A 1-year-old castrated male domestic shorthair cat was suspected with myasthenia gravis (MG) based on neurological examination, complete blood count (CBC), serum biochemistry, radiography and electrophysiological examination. In addition, a 9-year-old spayed female domestic shorthair cat was diagnosed with MG based on neurological examination, CBC, serum biochemistry, radiography, ultrasonography and increased acetylcholine receptor antibody titre. Positioning head tilt (PHT) was observed at the time of diagnosis in both cats. Relevance and novel information: Although the pathophysiology of PHT in cats is not fully understood, the mechanism for PHT in cats with MG may be similar to that of cats with hypokalaemic myopathy, supporting our hypothesis that muscle spindle dysfunction causes PHT.

Transplantation of autologous bone marrow-derived mononuclear cells into cerebrospinal fluid in a canine model of spinal cord injury.

Introduction: Spinal cord injury (SCI) is associated with severe dysfunction of nervous tissue, and repair via the transplantation of bone marrow-derived mononuclear cells (BM-MNCs) into cerebrospinal fluid yields promising results. It is essential to understand the underlying mechanisms; therefore, this study aimed to evaluate the regenerative potential of autologous BM-MNC transplantation in a canine model of acute SCI. Methods: Six dogs were included in this study, and SCI was induced using an epidural balloon catheter between L2 and L3, particularly in the area of the anterior longitudinal ligament. BM-MNC transplantation was performed, and T2-weighted magnetic resonance imaging (MRI) was conducted at specific time points (i.e., immediately after inducing SCI and at 1, 2, and 4 weeks after inducing SCI); moreover, the expression of growth-associated protein 43 (GAP-43) was evaluated. Results: MRI revealed that the signal intensity reduced over time in both BM-MNC-treated and control groups. However, the BM-MNC-treated group exhibited a significantly faster reduction than the control group during the early stages of SCI induction (BM-MNC-treated group: 4.82 ± 0.135 cm [day 0], 1.71 ± 0.134 cm [1 week], 1.37 ± 0.036 cm [2 weeks], 1.21 cm [4 weeks]; control group: 4.96 ± 0.211 cm [day 0], 2.49 ± 0.570 cm [1 week], 1.56 ± 0.045 cm [2 weeks], 1.32 cm [4 weeks]). During the early stages of treatment, GAP-43 was significantly expressed at the proximal end of the injured spinal cord in the BM-MSC-treated group, whereas it was scarcely expressed in the control group. Conclusions: In SCI, transplanted BM-MNCs can activate the expression of GAP-43, which is involved in axonal elongation (an important process in spinal cord regeneration). Thus, cell therapy with BM-MNCs can provide favorable outcomes in terms of better regenerative capabilities compared with other therapies.

Reduction of life-cycle CO2 emissions by expanding car-sharing services: A case study on Japan.

Carbon neutrality is a growing concern for all global economies. We considered the number of new and used cars registered during 2009-2018 in Japan and estimated the total number of private and shared cars, assuming that when owners abandoned their old cars, a certain percentage of the owners chose to use a car-sharing service (i.e., car rental service), instead of buying a new private car. We estimated the CO2 emissions generated during the manufacturing, driving, and disposal stages of cars, to analyze the impact of car sharing on CO2 emissions. Then, we determined the changes in the life-cycle CO2 emissions of all the cars for three car-sharing penetration rates (0, 5, and 100%), assuming that all the cars were gasoline-powered. Additionally, we analyzed how electric vehicles can optimize the proposed strategy. An increase in car-sharing services significantly reduced vehicular CO2 emissions; the decrease in CO2 emissions from private cars when owners switched to car services significantly exceeded the increase in the CO2 emissions associated with the increased number of cars. The proposed model can serve as a reliable framework to analyze the current status of CO2 emissions and simulate the future changes in car-sharing services.

Reversible positioning head tilt observed in 14 cats with hypokalaemic myopathy.

CASE SERIES SUMMARY: Positioning head tilt (PHT) is a dynamic neurological sign in which the head tilts to the opposite side to which it is moving. This sign is triggered in response to head movement and is thought to be due to the lack of inhibition of vestibular nuclei by the cerebellar nodulus and uvula (NU). The occurrence of PHT in animals has been suggested to be an indicator of NU dysfunction. Here, we describe the acute onset of PHT in 14 cats. All the cats were diagnosed with hypokalaemic myopathy caused by a range of pathologies. The PHT resolved along with other signs related to myopathy, such as cervical flexion and generalised weakness, after electrolyte correction in all cats. RELEVANCE AND NOVEL INFORMATION: Hypokalaemic myopathy was the likely cause of PHT in the present feline cases.

Case report: Presumptive subcutaneous malignant peripheral nerve sheath tumor with intracranial invasion and osteolysis in the posterior fossa of a dog.

A 13-year-old castrated male Toy Poodle presented with an acute vestibular disorder. Magnetic resonance imaging and computed tomography revealed a large oval space-occupying mass with skull destruction located from the subcutaneous tissue to the posterior fossa region. Histopathologically, the mass was a bundled growth of spindle-shaped mesenchymal tumor cells between the myofibrillar and collagen bundles. The cells were moderately irregular in size and had eosinophilic stained cytoplasm. The cells were highly atypical and had rare mitotic figures. Neoplastic cells were immunoreactive for S100, GFAP, Olig-2, SOX10 and immunonegative for NF, E-cadherin, and Claudin-1. Collective findings were presumptive with a diagnosis of malignant peripheral nerve sheath tumor.

Spinal epidural empyema concurrent with sequestrum in a cat: a case report.

A 5-month-old intact female mixed cat presented with repetitive paraplegia and drainage of pus from the back despite continuous antibiotic medication. Neurologic examination was consistent with below T3-L3 myelopathy. Computed tomography and magnetic resonance imaging revealed a contrast-enhanced mass in the L1-3 spinal canal, and bone fragments in the T13 and L1 spinal canal. Spinal epidural empyema was suspected, and hemilaminectomy was performed for T12-L2 on the right side and T11-12 on the left side. Bone fragments were diagnosed as sequestrum infected with Bacteroides sp. The cat recovered enough to ambulate next day. One month after surgery, there was no deficit in neurological function. This is the first report of spinal epidural empyema concurrent with sequestrum in a cat.

Expression of L-type amino acid transporter 1 in canine and feline intracranial tumors.

L-type amino acid transporter 1 (LAT1) is upregulated in various malignant tumors in humans. LAT1 expression correlates with the grade of cancer and prognosis. LAT1 is responsible for the supply of many essential amino acids to cancer cells. Inhibition of LAT1 reduces the amino acids that enter the cell and inhibits cancer cell growth. Therefore, novel anticancer drugs targeting LAT1 have attracted much attention in recent years. In this study, to explore the applicability of using LAT1 expression in intracranial tumors as a prognostic factor and therapeutic target, we investigated the expression of LAT1 in surgically resected primary and secondary intracranial tumor tissues from dogs and cats. Immunohistochemical analysis of LAT1 was performed on intracranial tumor tissue from 14 dogs and 3 cats. Primary intracranial tumors were seen in 10 dogs and included meningiomas, histiocytic sarcomas, pituitary tumors, and gliomas, and 9 out of 10 cases were positive for LAT1. Primary intracranial tumors were seen in 2 cats and included meningioma and lymphoma; both cases were positive for LAT1. Secondary intracranial tumors were positive for LAT1 in 3 out of 4 cases in dogs and 1 out of 1 in cats. Since the majority of intracranial tumors in dogs and cats were positive for LAT1, immunostaining for LAT1 is expected to be a prognostic indicator and therapeutic target in the future.

A case of feline temporal lobe epilepsy with hippocampal sclerosis and dentate gyrus malformation.

A two-months-old, male, mixed breed cat presented with epileptic seizures. The cat was diagnosed with drug-resistant epilepsy, and died at 3-years of age. No gross lesion was found at necropsy. Histopathologically, the dentate gyrus granule cell layer of the hippocampus was irregularly arranged. Granule cells were dispersed and ectopic cells were sporadically observed in the molecular layer. The granule cells had an enlarged cytoplasm and swollen nucleus. Immunohistochemistry for NeuN and GFAP confirmed severe neuronal loss and mild gliosis in CA1. Binucleation and ischemic change were observed in the remaining pyramidal cells. This report describes a case of feline temporal lobe epilepsy and hippocampal sclerosis associated with dentate gyrus malformation.

Case Report: Detection of Transferrin in a Dog Suspected of Having Cerebrospinal Fluid Rhinorrhea.

A 12-year-old Yorkshire terrier was referred for epileptic seizures and nasal discharge. The fluid was clear and serous. Cerebrospinal fluid (CSF) rhinorrhea was suspected, based on clinical signs and MRI findings. In humans, analysis of nasal secretions to determine the concentration of glucose and brain-type transferrin has been widely used clinically in order to confirm the presence of CSF rhinorrhea. The glucose concentration in the nasal discharge was 74 mg/dL. Serum-type and brain-type isoforms of transferrin were detectable in the nasal sample. The concentration of glucose and brain-type transferrin could be useful for diagnosing CSF rhinorrhea.

Positioning Head Tilt in Canine Lysosomal Storage Disease: A Retrospective Observational Descriptive Study.

Positioning head tilt is a neurological sign that has recently been described in dogs with congenital cerebellar malformations. This head tilt is triggered in response to head movement and is believed to be caused by a lack of inhibition of the vestibular nuclei by the cerebellar nodulus and ventral uvula (NU), as originally reported cases were dogs with NU hypoplasia. We hypothesized that other diseases, such as lysosomal storage diseases that cause degeneration in the whole brain, including NU, may cause NU dysfunction and positioning head tilt. Videos of the clinical signs of canine lysosomal storage disease were retrospectively evaluated. In addition, post-mortem NU specimens from each dog were histopathologically evaluated. Nine dogs were included, five with lysosomal storage disease, two Chihuahuas with neuronal ceroid lipofuscinosis (NCL), two Border Collies with NCL, one Shikoku Inu with NCL, two Toy Poodles with GM2 gangliosidosis, and two Shiba Inus with GM1 gangliosidosis. Twenty-eight videos recorded the clinical signs of the dogs. In these videos, positioning head tilt was observed in seven of nine dogs, two Chihuahuas with NCL, one Border Collie with NCL, one Shikoku Inu with NCL, one Toy Poodle with GM2 gangliosidosis, and two Shiba Inus with GM1 gangliosidosis. Neuronal degeneration and loss of NU were histopathologically confirmed in all diseases. As positioning head tilt had not been described until 2016, it may have been overlooked and may be a common clinical sign and pathophysiology in dogs with NU dysfunction.

Pathological changes within two weeks following spinal cord injury in a canine model.

PURPOSES: This study aimed to investigate the histopathological changes that occur within 2 weeks following spinal cord injury (SCI) in dogs. METHODS: Eight adult female Beagle dogs were included in this study, and SCI was induced using an epidural balloon catheter. Two dogs were killed at each of the following four time points: immediately after the procedure and 1 day, 1 week, and 2 weeks after the procedure. Neurological status was evaluated with five categories. Histopathological changes were visually observed for stained sections of formalin-fixed spinal cord to evaluate hemorrhage, spongiosis, necrosis, and gliosis morphologically. RESULTS: Along the 2 weeks post-injury, severe hemorrhage was observed at the primary injury site, the average diameter of which expanded quickly from 8 to 10 mm in 1 day and then decreased to 5 mm in 1 week. This indicates that the bleeding cavity expanded at the initial injury site to produce ascending and descending hemorrhage. The hemorrhage at the injury site resolved in 2 weeks. In contrast, spongiosis, parenchymal necrosis, and gliosis were first inconspicuous or mild and then became severe in 1 week or 2 weeks. Hemorrhage, hematoma, and other similar changes occurred at the regions approximately 20-mm rostral and caudal to the primary injury site. These changes were observed in both gray matter and white matter. CONCLUSIONS: This study is the first to assess the sequential histopathological changes in the acute and intermediate phases following SCI in dogs. Our findings enhance the usefulness of the canine intervertebral disk disease model in the assessment of secondary spinal cord histopathology in human SCI.

The NRG3/ERBB4 signaling cascade as a novel therapeutic target for canine glioma.

Canine glioma is a common brain tumor with poor prognosis despite surgery and/or radiation therapy. Therefore, newer and more effective treatment modalities are needed. Neuregulin 3 (NRG3) has known to be a ligand of ERBB4. This study aimed to investigate the usefulness of the NRG3/ERBB4 signaling cascade as a novel therapeutic target in canine glioma. We found out that microRNA (miR)-190a was downregulated in canine brain tumor tissues, including glioma and meningioma. miR-190a directly targeted NRG3 and inhibited the growth of canine glioma cells. The level of p-Akt, which is a downstream target of ERBB4 signaling, was decreased by transfection with miR-190a. NRG3 silencing also suppressed cell growth and decreased the levels of p-Akt and p-ERK1/2, and NRG3 overexpression exhibited opposed effects in canine glioma J3T-1 cells. The mRNA level of erbb4 was significantly upregulated in glioma tissues compared with that in normal brain tissues and meningioma tissues. Furthermore, compared with gefitinib and lapatinib, afatinib exerted a greater inhibitory effect on the growth of canine glioma cells. In conclusion, NRG3/ERBB4 signaling is negatively regulated by miR-190a and contributes to the growth of canine glioma cells, indicating that it may be a promising therapeutic target in canine glioma.

Outcomes of dogs with progressive myelomalacia treated with hemilaminectomy or with extensive hemilaminectomy and durotomy.

OBJECTIVE: To evaluate the ability of extensive hemilaminectomy and durotomy (EHLD) to control progressive myelomalacia (PMM) in dogs. STUDY DESIGN: Retrospective clinical study. ANIMALS: Twenty-eight client owned dogs that underwent EHLD (n = 10) or HL alone (n = 18). METHODS: After diagnosis by MRI, dogs were immediately treated with HL alone or EHLD at the site of intramedullary hyperintensity on T2-weighted (T2W)-MRI. Medical records were retrospectively reviewed. Follow-up data were collected via telephone interviews with the referring veterinarian and a standardized questionnaire. Postoperative survival outcome between groups was compared (log-rank test) by using Cox's proportional hazard analysis with baseline characteristics entered as covariates. RESULTS: The survival rate was higher in the EHLD group (P = .03) compared with the HL-alone group. Eleven of 18 dogs treated with HL survived, while seven of 18 dogs died (median, 5 days after surgery). In the EHLD group, 10 of 10 dogs survived postoperatively. Baseline characteristics were not associated with postoperative survival outcomes. According to multivariate analysis, EHLD was the independent factor associated with an increase in survival rate (P = .0002). CONCLUSION: EHLD durotomy at the intramedullary hyperintense region on T2W-MRI improved the survival rate of dogs with PMM compared with dogs treated with standard HL. CLINICAL SIGNIFICANCE: This study provides evidence that supports treatment with EHLD in dogs with PMM. Additional prospective studies are required.

Outcomes of extensive hemilaminectomy with durotomy on dogs with presumptive progressive myelomalacia: a retrospective study on 34 cases.

BACKGROUND: Progressive myelomalacia (PMM) is a fatal complication of progressive ascending and descending necrosis of the spinal cord after acute spinal cord injury. A recent study suggested that extensive hemilaminectomy with durotomy (EHLD) at the intramedullary T2-hyperintense region which performed immediately after magnetic resonance imaging (MRI) improved the survival rate in dogs with presumptive PMM. The objective of this retrospective study was to evaluate the effects of EHLD on halting the progression of PMM in dogs presumptively diagnosed with PMM which had the interval between MRI and surgery. RESULTS: Thirty-four dogs with presumptive PMM which had undergone EHLD with the delay following MRI examination (range, 0 to 3 days) were included. The cranial side of EHLD was set depending on the delay time after MRI, MRI findings, neurological examination and intraoperative macroscopic appearance. Two weeks after surgery, the perioperative survival rate was 97% (33/34). During follow-up with a median time period of 82.5 weeks (range, 0-290 weeks), the postoperative survival rate was 91% (31/34). At the end of the follow-up period, 31 out of 34 dogs were alive without severe postoperative complications while the remaining 2 dogs died from causes not directly attributable to the surgery. There was no improvement in the pelvic limb function of all dogs. CONCLUSIONS: EHLD appears to be effective in halting the progression of presumptive PMM and preventing morbidity even in dogs which had the interval between MRI and EHLD. Our algorithm of determining the range of EHLD may enable to set the appropriate ranges of EHLD in the cases which develop signs consistent with PMM after MRI examination.

Feline neurological diseases in a veterinary neurology referral hospital population in Japan.

Many of the reports summarizing neurological disorders in cats considered only a limited disease group(s). There is only one large-scale survey on neurological disorders in cats based on the histopathological viewpoint. We described the localizations and frequencies of neurological diseases in a large population of cats that were referred to the Kyoto Animal Referral Medical Center between 2009 and 2016. We attempted to determine the localization of lesions at the time of the examination in each case and to classify the disease etiologies of these 276 cats with neurological disorders retrospectively. There were 174 cases with lesions in the brain region, 14 cases with lesions in the cervical cord region, 34 cases with lesions in the thoracolumbar cord region, and 54 cases with lesions in the peripheral neuromuscular region. High morbidity rates were observed in cases of idiopathic epilepsy and intracranial tumor in the brain region, spinal cord infarction in the cervical cord region, spinal cord infarction and spinal cord tumor in the thoracolumbar cord region, and peripheral vestibular dysfunction arising from otitis media/interna in the peripheral neuromuscular region. It was suggested that there is a higher number of brain diseases than spinal cord and peripheral neuromuscular diseases in cats. Idiopathic and neoplastic diseases were common in the brain region, vascular diseases were common in the spinal cord region, and infectious diseases were common in the peripheral neuromuscular region.

Anaplastic oligodendroglioma with leptomeningeal dissemination in a french bulldog.

A 2.5-year-old male French Bulldog was evaluated for seizures. Cranial magnetic resonance imaging (MRI) suggested a glioma in the left piriform area. Radiation therapy (RT) and continuous chemotherapy were administered. Although the lesion had regressed significantly 2 months after RT, a follow-up MRI revealed meningeal enhancement in the left piriform area, which expanded further, with hydrocephalus, by day 310 (8 months after RT). Because of the poor prognosis, the dog was euthanized on day 356 and necropsy was performed. Histopathological examination confirmed anaplastic oligodendroglioma with leptomeningeal dissemination. This case suggests that the possibility of leptomeningeal dissemination and hydrocephalus should be considered even after RT and chemotherapy for anaplastic oligodendroglioma.

Role of vehicle inspection policy in climate mitigation: The case of Japan.

In 1951, the Japanese government introduced a vehicle safety inspection system and this system has an effect of shortening the 'economic' lifetimes of automobiles and increasing CO2 emissions associated with vehicle life-cycle. This study develops an integrated assessment framework by combining dynamic discrete choice analysis with life-cycle environmental accounting analysis based on a dynamic stock model. From the empirical results, we found that (1) the economic lifetime of a Prius in the benchmark model is surprisingly short, 5.07 years, due to the strict car inspection system, and this replacement cycle has contributed to increasing CO2 over time; and (2) abolishing car inspections at the third and fifth years would considerably contribute to reducing life-cycle CO2 emissions associated with Prius sold during the study period, 1997 to 2016, accounting for approximately one million tons-CO2 eq. over 20 years. Thus, we conclude that modifying the regulation policy with a focus on the car inspection system to induce car owners to keep their automobiles longer would have environmental benefits.

Head Tilting Elicited by Head Turning in Three Dogs with Hypoplastic Cerebellar Nodulus and Ventral Uvula.

The nodulus and ventral uvula (NU) of the cerebellum play a major role in vestibular function in humans and experimental animals; however, there is almost no information about NU function in the veterinary clinical literature. In this report, we describe three canine cases diagnosed with presumptive NU hypoplasia. Of them, one adult dog presented with cervical intervertebral disk disease, and two juvenile dogs presented with signs of central vestibular disease. Interestingly, an unusual and possibly overlooked neurological sign that we called "positioning head tilt" was observed in these dogs. The dogs were able to turn freely in any direction at will. The head was in a level position when static or when the dog walked in a straight line. However, the head was tilted to the opposite side when the dog turned. Veterinary clinicians should be aware of this neurological sign that has not been reported previously, and its application in lesion localization in dogs.

Case of a miniature dachshund with a primitive neuroectodermal tumor confined to the forebrain region treated with a combination of surgery and chemotherapy.

A miniature dachshund aged 9 years and 7 months with a history of polyuria/polydipsia and depression was referred. General physical and neurological examinations revealed no obvious abnormalities. MRI of the brain revealed a large space-occupying lesion in the left frontal lobe. This was surgically removed and pathologically diagnosed as a primitive neuroectodermal tumor (PNET). Although the clinical signs had been improved, follow-up MRI revealed recurrence of the tumor. Lomustine was administered, but 1 year after surgery, the dog exhibited cluster seizures and died. This is the first reported case of a dog with PNET confined to the forebrain region treated by surgical resection in combination with chemotherapy, as observed by repeated follow-up MRI.

In situ detection of GM1 and GM2 gangliosides using immunohistochemical and immunofluorescent techniques for auxiliary diagnosis of canine and feline gangliosidoses.

BACKGROUND: GM1 and GM2 gangliosidoses are progressive neurodegenerative lysosomal storage diseases resulting from the excessive accumulation of GM1 and GM2 gangliosides in the lysosomes, respectively. The diagnosis of gangliosidosis is carried out based on comprehensive findings using various types of specimens for histological, ultrastructural, biochemical and genetic analyses. Therefore, the partial absence or lack of specimens might have resulted in many undiagnosed cases. The aim of the present study was to establish immunohistochemical and immunofluorescent techniques for the auxiliary diagnosis of canine and feline gangliosidoses, using paraffin-embedded brain specimens stored for a long period. RESULTS: Using hematoxylin and eosin staining, cytoplasmic accumulation of pale to eosinophilic granular materials in swollen neurons was observed in animals previously diagnosed with GM1 or GM2 gangliosidosis. The immunohistochemical and immunofluorescent techniques developed in this study clearly demonstrated the accumulated material to be either GM1 or GM2 ganglioside. CONCLUSIONS: Immunohistochemical and immunofluorescent techniques using stored paraffin-embedded brain specimens are useful for the retrospective diagnosis of GM1 and GM2 gangliosidoses in dogs and cats.