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Introduction: Canine meningoencephalitis of unknown origin (MUO) is a debilitating disease associated with high mortality. The prognostic value of magnetic resonance imaging (MRI) findings for predicting survival at 12 months and long-term relapse remains uncertain. Methods: This was a retrospective cohort study evaluating the prognostic value of different MRI variables using multivariable logistic regression and Cox proportional hazards analysis. Results: In total, 138 dogs were presumptively diagnosed with MUO. The most common location for lesions identified on MRI were the white matter tracts of the corona radiata and corpus callosum, followed by the frontal, sensorimotor and temporal cortices. Lower T2 lesion load (p = 0.006, OR = 0.942, CI = 0.902-0.983) was associated with longer survival and higher T1 post-contrast lesion load (p = 0.023, OR = 1.162, CI = 1.021-1.322) was associated with relapse. Discussion: This study has identified prognostic factors that may help identify dogs at higher risk of death and relapse and therefore guide treatment recommendations. [ABSTRACT FROM AUTHOR]

Abstract Background The information relating to the outcome specifically for juvenile dogs with meningoencephalitis of unknown etiology (MUE) is lacking. Objectives To describe the clinical presentation, diagnostic findings, treatment, and outcome in a cohort of dogs with MUE

Abstract Background Meningoencephalitis of unknown origin (MUO) comprises a group of noninfectious inflammatory diseases affecting the central nervous system of dogs. Previous studies have reported individual risk factors for survival but prognostication for MUO remains challenging. Objectives Identify clinical prognostic variables in dogs with MUO. Animals A retrospective study of 447 dogs presented to 2 UK referral hospitals and diagnosed with MUO. Methods Medical records of dogs diagnosed with MUO were retrospectively reviewed. Multivariable logistic regression was used for the identification of risk factors for survival and Cox proportional hazards analysis for the identification of risk factors for clinical relapse. Results Eighty‐two percent (366/447) of dogs with presumptive MUO survived to discharge and 63.5% (284/447) were alive at 6 months; 36% of the latter (103/284) had persistent neurological deficits. Breed (pugs; P = .03), epileptic seizures (P

Background: The information relating to the outcome specifically for juvenile dogs with meningoencephalitis of unknown etiology (MUE) is lacking. Objectives: To describe the clinical presentation, diagnostic findings, treatment, and outcome in a cohort of dogs with MUE <52 weeks old. Animals: Thirty‐four client‐owned dogs. Methods: Multicenter retrospective case series. Records from 5 referral centers were searched. Data was extracted from the medical records and referring veterinarians were contacted for survival data if this was not available from the record. Results: The mean age was 31 weeks; the youngest dog was 11 weeks and 3 dogs were <16 weeks old. Altered mentation (71%), ataxia (44%), seizures (29%), and circling (26%) were the most common presenting complaints. Neuroanatomical localization was to the forebrain (38%), multifocal (35%), brainstem (18%), and cerebellum (12%). Corticosteroid monotherapy (n = 15) and corticosteroid plus cytosine arabinoside (n = 15) were used in equal proportions. Outcome data was available for 26 dogs, 8 (31%) were alive at the time of data collection with a follow‐up range of 135 to 2944 days. Death or euthanasia was related to MUE in 17/18 dogs that died during the study period. Kaplan‐Meier survival analysis demonstrated a median survival time for all‐cause death of 84 days. Conclusion: The prognosis for MUE in this subset of dogs was considered poor. [ABSTRACT FROM AUTHOR]

Background: Meningoencephalitis of unknown origin (MUO) comprises a group of noninfectious inflammatory diseases affecting the central nervous system of dogs. Previous studies have reported individual risk factors for survival but prognostication for MUO remains challenging. Objectives: Identify clinical prognostic variables in dogs with MUO. Animals: A retrospective study of 447 dogs presented to 2 UK referral hospitals and diagnosed with MUO. Methods: Medical records of dogs diagnosed with MUO were retrospectively reviewed. Multivariable logistic regression was used for the identification of risk factors for survival and Cox proportional hazards analysis for the identification of risk factors for clinical relapse. Results: Eighty‐two percent (366/447) of dogs with presumptive MUO survived to discharge and 63.5% (284/447) were alive at 6 months; 36% of the latter (103/284) had persistent neurological deficits. Breed (pugs; P =.03), epileptic seizures (P <.001), paresis (P <.001), and higher neurodisability scale (NDS) score (P <.001) at presentation were negatively associated with survival to 6 months. Dogs with persistent deficits had higher NDS scores on presentation (P =.001). Median follow‐up time was 11 months (interquartile range [IQR], 1‐24) and 50.6% (160/316) relapsed during treatment (median time to relapse, 7 months; IQR, 2‐15). Incomplete resolution of the clinical signs during the 6 months after diagnosis (P <.001), higher NDS score (P <.001), and longer duration of the clinical signs (P <.001) were associated with relapse. Conclusions and Clinical Importance: Knowledge of risk factors associated with survival, incomplete recovery and clinical relapse in MUO can help guide monitoring and treatment and improve owner communications regarding prognosis for this debilitating disease. [ABSTRACT FROM AUTHOR]

Summary: In this review, we delve into the intricate relationship between white adipose tissue (WAT) remodeling and metabolic aspects in obesity, with a specific focus on individuals with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). WAT is a highly heterogeneous, plastic, and dynamically secreting endocrine and immune organ. WAT remodeling plays a crucial role in metabolic health, involving expansion mode, microenvironment, phenotype, and distribution. In individuals with MHO, WAT remodeling is beneficial, reducing ectopic fat deposition and insulin resistance (IR) through mechanisms like increased adipocyte hyperplasia, anti‐inflammatory microenvironment, appropriate extracellular matrix (ECM) remodeling, appropriate vascularization, enhanced WAT browning, and subcutaneous adipose tissue (SWAT) deposition. Conversely, for those with MUO, WAT remodeling leads to ectopic fat deposition and IR, causing metabolic dysregulation. This process involves adipocyte hypertrophy, disrupted vascularization, heightened pro‐inflammatory microenvironment, enhanced brown adipose tissue (BAT) whitening, and accumulation of visceral adipose tissue (VWAT) deposition. The review underscores the pivotal importance of intervening in WAT remodeling to hinder the transition from MHO to MUO. This insight is valuable for tailoring personalized and effective management strategies for patients with obesity in clinical practice. [ABSTRACT FROM AUTHOR]

A 2.5-year-old female entire Pomeranian dog was presented for acute paraparesis progressing within 2 days to paraplegia. General physical examination was unremarkable. Neurological examination showed paraplegia without nociception, a mass reflex upon testing perineal reflexes and withdrawal reflexes in the pelvic limbs and patellar hyperreflexia. Cutaneous trunci reflexes were absent caudal to the level of the 6th thoracic vertebra. Spinal hyperesthesia was present. Neuroanatomical localization was consistent with a T3-L3 myelopathy. Hematological and biochemical blood tests [including C-reactive protein (CRP)] were within reference ranges. MRI of the spinal cord from the level of the 1st thoracic vertebra to the sacrum revealed a patchy, ill-defined, moderate to marked T2W hyperintense, contrast enhancing intramedullary lesion extending from T1 to L4. Medical treatment based on a working diagnosis of meningomyelitis of unknown cause was initiated with corticosteroids and methadone based on pain scores. Prognosis was grave and after 3 days without return of nociception, the dog was euthanized according to the owners' wishes. Post-mortem histopathological examination of the brain and spinal cord yielded a morphological diagnosis of severe, segmental, bilateral and fairly symmetrical, necrotizing lymphohistiocytic leukomyelitis, with a non- suppurative angiocentric leptomeningitis. Some minor, focal, lymphocytic perivascular cuffing was found in the medulla oblongata as well, but otherwise there were no signs of brain involvement. No infectious causes were identified with ancillary tests. This case report underlines the importance of including meningomyelitis in the differential diagnosis list of dogs presented for acute progressive neurological signs referable to a myelopathy. [ABSTRACT FROM AUTHOR]

Purpose: Malignant ureteric obstruction is a significant management challenge. The failure of ureteric stents often leads to long-term nephrostomy tubes. This is delayed for as long as possible due to its’ associated morbidity. Several types of ureteric stents are available, however there is little evidence demonstrating which stents are better for preventing progression to nephrostomy tubes. This study looked to determine whether a new 6 French (Fr) polymer stent, 8Fr polymer stent or metallic stent achieved a longer functional duration once the initial polymer ureteric stent failed. Methods: A retrospective, longitudinal study was performed at a single tertiary institution. All patients who underwent ureteric stenting with a 6Fr polymer stent for malignancy between 2010 and 2020 were included. Patients were followed up until death with ureteric stent in situ or permanent nephrostomy tube insertion. Results: A total of 46 patients (66 ureters) had ureteric stents inserted for malignancy. From initial ureteric stent failure, 10 stents were changed to a new 6Fr polymer stent, 42 were changed to an 8Fr polymer stent and 14 were changed to a Resonance® 6Fr metallic stent. The Resonance 6Fr metallic stent had the longest median functional duration of 14 months (p = 0.012). Conclusion: Resonance® 6Fr metallic stents appear to have a significantly longer functional duration than a new 6Fr polymer stent or 8Fr polymer stent, which may allow patients to enjoy a better quality of life and delay permanent nephrostomy tube insertion. [ABSTRACT FROM AUTHOR]

A 2.5-year-old female entire Pomeranian dog was presented for acute paraparesis progressing within 2 days to paraplegia. General physical examination was unremarkable. Neurological examination showed paraplegia without nociception, a mass reflex upon testing perineal reflexes and withdrawal reflexes in the pelvic limbs and patellar hyperreflexia. Cutaneous trunci reflexes were absent caudal to the level of the 6th thoracic vertebra. Spinal hyperesthesia was present. Neuroanatomical localization was consistent with a T3-L3 myelopathy. Hematological and biochemical blood tests [including C-reactive protein (CRP)] were within reference ranges. MRI of the spinal cord from the level of the 1st thoracic vertebra to the sacrum revealed a patchy, ill-defined, moderate to marked T2W hyperintense, contrast enhancing intramedullary lesion extending from T1 to L4. Medical treatment based on a working diagnosis of meningomyelitis of unknown cause was initiated with corticosteroids and methadone based on pain scores. Prognosis was grave and after 3 days without return of nociception, the dog was euthanized according to the owners’ wishes. Post-mortem histopathological examination of the brain and spinal cord yielded a morphological diagnosis of severe, segmental, bilateral and fairly symmetrical, necrotizing lymphohistiocytic leukomyelitis, with a non-suppurative angiocentric leptomeningitis. Some minor, focal, lymphocytic perivascular cuffing was found in the medulla oblongata as well, but otherwise there were no signs of brain involvement. No infectious causes were identified with ancillary tests. This case report underlines the importance of including meningomyelitis in the differential diagnosis list of dogs presented for acute progressive neurological signs referable to a myelopathy.

IntroductionCanine meningoencephalitis of unknown origin (MUO) is a debilitating disease associated with high mortality. The prognostic value of magnetic resonance imaging (MRI) findings for predicting survival at 12 months and long-term relapse remains uncertain.MethodsThis was a retrospective cohort study evaluating the prognostic value of different MRI variables using multivariable logistic regression and Cox proportional hazards analysis.ResultsIn total, 138 dogs were presumptively diagnosed with MUO. The most common location for lesions identified on MRI were the white matter tracts of the corona radiata and corpus callosum, followed by the frontal, sensorimotor and temporal cortices. Lower T2 lesion load (p = 0.006, OR = 0.942, CI = 0.902–0.983) was associated with longer survival and higher T1 post-contrast lesion load (p = 0.023, OR = 1.162, CI = 1.021–1.322) was associated with relapse.DiscussionThis study has identified prognostic factors that may help identify dogs at higher risk of death and relapse and therefore guide treatment recommendations.

Abstract Background Meningoencephalitis of unknown origin is a common cause of severe neurological disease in dogs. The term covers a heterogeneous group of noninfectious inflammatory diseases, with immune dysregulation widely accepted as the underlying disease mechanism. Current treatment consists of immunosuppression, with corticosteroids being the mainstay of virtually all treatment regimens. However, side effects of corticosteroids can be severe, and might be the cause of death in some patients. This retrospective, multi-centric study aimed at describing a population of Scandinavian dogs with meningoencephalitis of unknown origin in regards to reported side effects and cause of death, and to highlight possible differences in survival, when comparing corticosteroid monotherapy with other treatment regimens. Results Within the 5-year study period, 63 dogs were included. Of these, 35 (49.3%) died or were euthanized during the study period. Median survival time from time of diagnosis based on Kaplan-Meier curves for the overall population was 714 days (equivalent to around 25 months, range 0-1678 days). There was no statistically significant difference (P = 0.31) in survival between dogs treated with corticosteroid monotherapy (n = 26, median survival time 716 days, equivalent to around 25 months, range 5–911 days), dogs receiving a combination of corticosteroids and ciclosporin (n = 15, median survival time 916 days, equivalent to around 31 months, range 35–1678 days), and dogs receiving corticosteroids combined with either cytosine arabinoside, leflunomide, or a combination of 2 or more add-on drugs (n = 13, median survival time 1186 days, equivalent to around 40 months, range 121–1640 days). Side effects were registered for 47/63 dogs. Polyphagia (n = 37/47), polyuria/polydipsia (n = 37/47), diarrhea (n = 29/47) and lethargy (n = 28/47) were most frequently reported. The most common cause for euthanasia was relapse (n = 15/35, 42.9%), followed by insufficient or lack of treatment response (n = 9, 25.7%). Side effects were the direct cause of euthanasia in 2/35 dogs (5.7%). Conclusions A large proportion of dogs in the overall population were euthanized due to relapse, emphasizing a need for treatment regimens aimed at specifically preventing relapse for an improved long-term survival. Side effects in dogs receiving corticosteroid monotherapy were rarely a direct cause of death, but were reported for all dogs. No statistically significant difference in survival was found when corticosteroid monotherapy was compared to other treatment regimens.

Abstract Background The terms metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) categorize subjects with obesity based on the presence or absence of cardio-metabolic risk factors. Detecting MUO phenotype is crucial due to the high risk of cardio-metabolic complications, requiring tailored and intensive follow-up. However, diagnosing MUO is time-consuming and costly. Thus, we aimed to investigate the role of Mediterranean diet (MD) in determining MHO/MUO phenotypes and whether adherence to MD could serve as an additional screening tool for MUO phenotype. Methods The study population of this cross-sectional observational study consisted of 275 subjects with obesity. We assessed their lifestyle habits (physical activity and smoking habits), anthropometric measurements (weight, height, waist circumference, body mass index), blood pressure, metabolic parameters, inflammatory marker (high sensitivity C reactive protein levels), adherence to MD (by PREvención con DIetaMEDiterránea (PREDIMED) questionnaire), and MHO/MUO phenotypes. Results The study included 275 individuals with obesity (256F/19M; 34.0 ± 10.5 years; BMI 38.3 ± 5.95 kg/m2). Among them, 114 (41.5%) exhibited MHO phenotype, while 161 (58.5%) had MUO phenotype. MHO phenotype exhibited favorable anthropometric and cardio-metabolic profiles, characterized by lower waist circumference (p

Abstract Background Neurofilament light chain (NfL) is an axonal cytoplasmic protein in neurons. Recently, NfL has shown potential as a diagnostic biomarker in dogs with meningoencephalitis of unknown origin (MUO). However, there have been no studies on the biomarkers of lesion progression and resolution in MUO. Objectives To identify the potential of NfL as a biomarker for predicting changes in lesions. Methods Seven dogs with MUO who had undergone two magnetic resonance imaging (MRI) scans were included. The serum NfL levels were measured using a single‐molecule array. The relationship between the rate of change in lesion size and the rate of change in serum NfL level was analysed using simple linear regression. To investigate the effect of changes in lesion size on NfL levels, the dogs were divided into two groups depending on the change in lesion size: decreased lesion size group (n = 5) and increased lesion size group (n = 2). Trends in lesion size change were identified in the second MRI compared with the first MRI. Results A significant positive relationship between the rate of lesion size change and the rate of NfL level change was identified (R2 = 0.9239, p = 0.0006). In the decreased lesion size group (n = 5), all NfL levels in each dog decreased, and in the increased lesion size group (n = 2), all NfL levels in each dog increased. Conclusions This preliminary study showed a positive relationship between the rate of change in lesion size and rate of change in serum NfL levels. Therefore, the serum NfL level may be a promising biomarker of lesion progression and resolution in MUO.

Abstract Background Meningoencephalitis of unknown origin (MUO) comprises a group of debilitating inflammatory diseases affecting the central nervous system of dogs. Currently, no validated clinical scale is available for the objective assessment of MUO severity. Objectives Design a neurodisability scale (NDS) to grade clinical severity and determine its reliability and whether or not the score at presentation correlates with outcome. Animals One hundred dogs with MUO were included for retrospective review and 31 dogs were subsequently enrolled for prospective evaluation. Methods Medical records were retrospectively reviewed for 100 dogs diagnosed with MUO to identify the most frequent neurological examination findings. The NDS was designed based on these results and evaluated for prospective and retrospective use in a new population of MUO patients (n = 31) by different groups of independent blinded assessors, including calculation of interobserver agreement and association with outcome. Results The most common clinical signs in MUO patients were used to inform categories for scoring in the NDS: seizure activity, ambulatory status, posture and cerebral, cerebellar, brainstem, and visual functions. The intraclass correlation coefficient (ICC) for prospective use of the NDS was 0.83 (95% confidence interval [CI], 0.68‐0.91) indicating good agreement, and moderate agreement was found between prospective and retrospective assessors (ICC, 0.71; 95% CI, 0.56‐0.83). No association was found between NDS score and long‐term outcome. Conclusions and Clinical Importance The NDS is a novel clinical measure for objective assessment of neurological dysfunction and showed good reliability when used prospectively in MUO patients but, in this small population, no association with outcome could be identified.

Background: Meningoencephalitis of unknown origin is a common cause of severe neurological disease in dogs. The term covers a heterogeneous group of noninfectious inflammatory diseases, with immune dysregulation widely accepted as the underlying disease mechanism. Current treatment consists of immunosuppression, with corticosteroids being the mainstay of virtually all treatment regimens. However, side effects of corticosteroids can be severe, and might be the cause of death in some patients. This retrospective, multi-centric study aimed at describing a population of Scandinavian dogs with meningoencephalitis of unknown origin in regards to reported side effects and cause of death, and to highlight possible differences in survival, when comparing corticosteroid monotherapy with other treatment regimens. Results: Within the 5-year study period, 63 dogs were included. Of these, 35 (49.3%) died or were euthanized during the study period. Median survival time from time of diagnosis based on Kaplan-Meier curves for the overall population was 714 days (equivalent to around 25 months, range 0-1678 days). There was no statistically significant difference (P = 0.31) in survival between dogs treated with corticosteroid monotherapy (n = 26, median survival time 716 days, equivalent to around 25 months, range 5–911 days), dogs receiving a combination of corticosteroids and ciclosporin (n = 15, median survival time 916 days, equivalent to around 31 months, range 35–1678 days), and dogs receiving corticosteroids combined with either cytosine arabinoside, leflunomide, or a combination of 2 or more add-on drugs (n = 13, median survival time 1186 days, equivalent to around 40 months, range 121–1640 days). Side effects were registered for 47/63 dogs. Polyphagia (n = 37/47), polyuria/polydipsia (n = 37/47), diarrhea (n = 29/47) and lethargy (n = 28/47) were most frequently reported. The most common cause for euthanasia was relapse (n = 15/35, 42.9%), followed by insufficient or lack of treatment response (n = 9, 25.7%). Side effects were the direct cause of euthanasia in 2/35 dogs (5.7%). Conclusions: A large proportion of dogs in the overall population were euthanized due to relapse, emphasizing a need for treatment regimens aimed at specifically preventing relapse for an improved long-term survival. Side effects in dogs receiving corticosteroid monotherapy were rarely a direct cause of death, but were reported for all dogs. No statistically significant difference in survival was found when corticosteroid monotherapy was compared to other treatment regimens. [ABSTRACT FROM AUTHOR]

Background: The terms metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) categorize subjects with obesity based on the presence or absence of cardio-metabolic risk factors. Detecting MUO phenotype is crucial due to the high risk of cardio-metabolic complications, requiring tailored and intensive follow-up. However, diagnosing MUO is time-consuming and costly. Thus, we aimed to investigate the role of Mediterranean diet (MD) in determining MHO/MUO phenotypes and whether adherence to MD could serve as an additional screening tool for MUO phenotype. Methods: The study population of this cross-sectional observational study consisted of 275 subjects with obesity. We assessed their lifestyle habits (physical activity and smoking habits), anthropometric measurements (weight, height, waist circumference, body mass index), blood pressure, metabolic parameters, inflammatory marker (high sensitivity C reactive protein levels), adherence to MD (by PREvención con DIetaMEDiterránea (PREDIMED) questionnaire), and MHO/MUO phenotypes. Results: The study included 275 individuals with obesity (256F/19M; 34.0 ± 10.5 years; BMI 38.3 ± 5.95 kg/m2). Among them, 114 (41.5%) exhibited MHO phenotype, while 161 (58.5%) had MUO phenotype. MHO phenotype exhibited favorable anthropometric and cardio-metabolic profiles, characterized by lower waist circumference (p < 0.001), BMI (p < 0.001), insulin resistance (p < 0.001), blood pressure (p < 0.001), inflammation (p < 0.001), and lipid levels (p < 0.001) compared to MUO phenotype. Notably, we found that MHO phenotype had higher adherence to MD (p < 0.001) and consumed more extra virgin olive oil (EVOO) (p < 0.001), vegetables (p < 0.001), fruits (p < 0.001), legumes (p = 0.001), fish (p < 0.001), wine (p = 0.008), and nuts (p = 0.001), while reporting lower intake of red/processed meats (p < 0.001), butter, cream, margarine (p = 0.008), soda drinks (p = 0.006), and commercial sweets (p = 0.002) compared to MUO phenotype. Adherence to MD (p < 0.001) and EVOO (p = 0.015) intake were identified as influential factors in determining the presence of MUO/MHO phenotypes. Furthermore, a PREDIMED score < 5 proved to be the most sensitive and specific cut-point value for predicting the presence of MUO phenotype (p < 0.001). Conclusion: High adherence to MD was associated with MHO phenotype. Moreover, we suggest that a specific cut-off of the PREDIMED score could be an indicator to discriminate patients with MUO/MHO phenotypes and therefore help in identifying patients at higher cardiovascular risk who will require specific dietary intervention. [ABSTRACT FROM AUTHOR]

Simple Summary: Steroid-responsive meningitis-arteritis (SRMA) is a common immune-mediated inflammatory disease of young-adult dogs with predominantly neck pain and fever. The exact pathomechanism of this disease remains unclear. Interleukin-31 is a cytokine that has been shown to be elevated among other things in dogs with atopic dermatitis and dogs with a typical phenotype of inflammation (Th2-mediated) in previous studies. This phenotype of inflammation is typical for SRMA. Therefore, we suggested that interleukin-31 might be involved in the pathomechanism of SRMA. Within the study, interleukin-31 levels were measured in serum and cerebrospinal fluid samples of dogs affected by SRMA in comparison to dogs with atopic dermatitis (positive control), healthy dogs (negative control) and dogs with immune-mediated or infectious meningoencephalitis. The serum interleukin-31 levels of dogs with SRMA were markedly higher than in healthy control dogs. Especially dogs with SRMA without any pre-treatment showed markedly higher interleukin-31 levels. The cerebrospinal fluid interleukin-31 levels revealed no differences between the groups. Based on this study, an involvement of interleukin-31 in the pathogenesis of SRMA can be assumed, but further clarification is necessary with prospective studies. We suggest that our study might help to clarify further parts of the pathogenesis of SRMA. Steroid-responsive meningitis-arteritis (SRMA) is a predominantly Th-2 immune-mediated disease, but the exact pathomechanism remains unclear. Interleukin-31 (IL-31) is predominantly produced by T cells with a Th-2 phenotype during proinflammatory conditions. We hypothesize that IL-31 might be involved in the pathogenesis of SRMA. IL-31 was measured in archived samples (49 serum and 52 CSF samples) of dogs with SRMA, meningoencephalitis of unknown origin (MUO), infectious meningoencephalitis, and atopic dermatitis, and of healthy control dogs using a competitive canine IL-31 ELISA. The mean serum IL-31 level in dogs with SRMA (n = 18) was mildly higher compared to dogs with atopic dermatitis (n = 3, p = 0.8135) and MUO (n = 15, p = 0.7618) and markedly higher than in healthy controls (n = 10, p = 0.1327) and dogs with infectious meningoencephalitis (n = 3, no statistics). Dogs with SRMA in the acute stage of the disease and without any pre-treatment had the highest IL-31 levels. The mean CSF IL-31 value for dogs with SRMA (n = 23) was quite similar to that for healthy controls (n = 8, p = 0.4454) and did not differ markedly from dogs with MUO (n = 19, p = 0.8724) and infectious meningoencephalitis. Based on this study, an involvement of IL-31 in the pathogenesis of the systemic Th-2 immune-mediated immune response in SRMA can be assumed as a further component leading to an aberrant immune reaction. [ABSTRACT FROM AUTHOR]

Background: Neurofilament light chain (NfL) is an axonal cytoplasmic protein in neurons. Recently, NfL has shown potential as a diagnostic biomarker in dogs with meningoencephalitis of unknown origin (MUO). However, there have been no studies on the biomarkers of lesion progression and resolution in MUO. Objectives: To identify the potential of NfL as a biomarker for predicting changes in lesions. Methods: Seven dogs with MUO who had undergone two magnetic resonance imaging (MRI) scans were included. The serum NfL levels were measured using a single‐molecule array. The relationship between the rate of change in lesion size and the rate of change in serum NfL level was analysed using simple linear regression. To investigate the effect of changes in lesion size on NfL levels, the dogs were divided into two groups depending on the change in lesion size: decreased lesion size group (n = 5) and increased lesion size group (n = 2). Trends in lesion size change were identified in the second MRI compared with the first MRI. Results: A significant positive relationship between the rate of lesion size change and the rate of NfL level change was identified (R2 = 0.9239, p = 0.0006). In the decreased lesion size group (n = 5), all NfL levels in each dog decreased, and in the increased lesion size group (n = 2), all NfL levels in each dog increased. Conclusions: This preliminary study showed a positive relationship between the rate of change in lesion size and rate of change in serum NfL levels. Therefore, the serum NfL level may be a promising biomarker of lesion progression and resolution in MUO. [ABSTRACT FROM AUTHOR]

Simple Summary: Crisdesalazine is a multi-targeted drug with antioxidant and anti-inflammatory action to prevent amyloid plaque, neurofibrillary tangle, and neurodegeneration that cause dementia. We tried this drug on meningoencephalitis of unknown origin in dogs, expecting the improvement of their neurologic signs. In Case 1, the dog was tentatively diagnosed with meningoencephalitis of unknown origin by MRI and has started treatment with prednisolone and cytarabine. However, recurrent severe bacterial cystitis has occurred, suspected as the side effect of immunosuppressants. After adding crisdesalazine in ongoing therapy, the patient could reduce the dosage of the drugs successfully. In Case 2, the dog was tentatively diagnosed with meningoencephalitis of unknown origin through its history using clinical signs, blood analysis, neurologic examination, magnetic resonance imaging, and cerebrospinal fluid analysis. The dog has started treatment with cytarabine, prednisolone, and levetiracetam and the alleviation of the clinical signs was inadequate. However, after adding crisdesalazine in ongoing treatment, the neurologic signs of the dog were markedly improved. To the best of our knowledge, no previous report has documented clinical cases of reduced neurological signs in dogs with meningoencephalitis of unknown origin after adding crisdesalazine as an adjunct to ongoing immunosuppressive treatment. An 8-year-old, castrated male Shih-tzu dog (Case 1) showing ataxia and gait disorder was referred for neurological examination and magnetic resonance imaging. Through comprehensive examinations, the patient was tentatively diagnosed with meningoencephalitis of unknown origin (MUO) and treatment with prednisolone and cytosine arabinoside was started. The symptoms were improving with immunosuppressive treatment. However, severe bacterial cystitis occurred and we could not avoid tapering off prednisolone. Then, neurological signs recurred. Therefore, we added crisdesalazine, which allowed us to reduce the daily dosage of immunosuppressants easily. In another case, a 4-year-old, spayed female Yorkshire terrier dog (Case 2) was referred to our hospital showing a head tilt, circling, and loss of the menace reflex. The patient was tentatively diagnosed with MUO and treatment with some immunosuppressants was attempted. The clinical symptoms improved, but the alleviation was inadequate. Thus, we added crisdesalazine. The neurological signs then markedly improved. Moreover, the drugs could be tapered off more easily than before. Crisdesalazine is a novel drug that has antioxidant and anti-inflammatory action in brain disease and is used particularly for dementia. In this paper, we tried an off-label use of this drug in canine MUO patients, and found that it had, in these two patients, additional therapeutic effects on the MUO. [ABSTRACT FROM AUTHOR]

Background: Meningoencephalitis of unknown origin (MUO) comprises a group of debilitating inflammatory diseases affecting the central nervous system of dogs. Currently, no validated clinical scale is available for the objective assessment of MUO severity. Objectives: Design a neurodisability scale (NDS) to grade clinical severity and determine its reliability and whether or not the score at presentation correlates with outcome. Animals: One hundred dogs with MUO were included for retrospective review and 31 dogs were subsequently enrolled for prospective evaluation. Methods: Medical records were retrospectively reviewed for 100 dogs diagnosed with MUO to identify the most frequent neurological examination findings. The NDS was designed based on these results and evaluated for prospective and retrospective use in a new population of MUO patients (n = 31) by different groups of independent blinded assessors, including calculation of interobserver agreement and association with outcome. Results: The most common clinical signs in MUO patients were used to inform categories for scoring in the NDS: seizure activity, ambulatory status, posture and cerebral, cerebellar, brainstem, and visual functions. The intraclass correlation coefficient (ICC) for prospective use of the NDS was 0.83 (95% confidence interval [CI], 0.68‐0.91) indicating good agreement, and moderate agreement was found between prospective and retrospective assessors (ICC, 0.71; 95% CI, 0.56‐0.83). No association was found between NDS score and long‐term outcome. Conclusions and Clinical Importance: The NDS is a novel clinical measure for objective assessment of neurological dysfunction and showed good reliability when used prospectively in MUO patients but, in this small population, no association with outcome could be identified. [ABSTRACT FROM AUTHOR]

Background: The current study aimed to screen for relationships and different potential metabolic biomarkers involved between metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) in adolescents. Methods: The study included 148 obese adolescents aged between 14 and 16. The study participants were divided into MUO and MHO groups based on the age-specific adolescent metabolic syndrome (MetS) criteria of the International Diabetes Federation. The current study was conducted to investigate the clinical and metabolic differences between the MHO and MUO groups. Multivariate analyses were conducted to investigate the metabolites as independent predictors for the odds ratio and the presence of the MetS. Results: There were significant differences in the three acylcarnitines, five amino acids, glutamine/glutamate ratio, three biogenic amines, two glycerophospholipids, and the triglyceride-glucose index between the MUO group and those in the MHO group. Moreover, several metabolites were associated with the prevalence of MUO. Additionally, several metabolites were inversely correlated with MHO in the MUO group. Conclusions: In this study, the biomarkers found in this study have the potential to reflect the clinical outcomes of the MUO group. These biomarkers will lead to a better understanding of MetS in obese adolescents. [ABSTRACT FROM AUTHOR]

IntroductionA variety of treatment options have been described for canine meningoencephalitis of unknown origin (MUO). Few studies focused on radiation therapy as a second line immunomodulating treatment, implicating its effective use. However, a standard radiation therapy protocol is lacking, and further research will help to evaluate the effect of different dose regimens.MethodsTen dogs diagnosed with MUO based on MRI and CSF findings were prospectively enrolled. The dogs were treated with a shortened whole brain radiation therapy protocol (5 × 4 Gy) in combination with prednisolone. Neurologic changes were quantified using an established scoring scheme. Follow-up MRI and CSF examination was scheduled three months after radiation therapy. Overall survival and time to progression were calculated. Histopathology of the brain was performed in case of death.ResultsSeven dogs were diagnosed de novo and three had a history of relapsing MUO. Neurological status improved in all 10 dogs during radiation therapy, with 4/10 returning to normal shortly after radiation therapy. Three dogs died within the first three months after radiation therapy. At follow-up MRI lesions completely resolved in two dogs, partially resolved in five dogs, and progressed in one dog. After follow-up MRI, dogs were further treated with prednisolone monotherapy (two dogs) and additional immunosuppressant drugs (five dogs). Overall, four dogs showed disease progression, with a mean time to progression of 691 days (95%CI: 396–987) and mean overall survival for all dogs was 723 days (95%CI: 436–1011) (both medians not reached). Histopathology confirmed MUO in three dogs but was suggestive for oligodendroglioma in one dog. Radiation induced side effects were not seen.ConclusionShortened whole-brain radiation therapy could be an additional treatment option for MUO in conjunction to prednisolone, specifically for cases that require rapid relief of symptoms and with relapsing history.

This document is a corrigendum for an article titled "Magnetic resonance imaging prognostic factors for survival and relapse in dogs with meningoencephalitis of unknown origin." The corrigendum acknowledges an error in the original article, where the authors failed to acknowledge support from a different department within the university. The corrected sentence has been added to the acknowledgments section. The authors apologize for the error and state that it does not change the scientific conclusions of the article. The corrigendum also includes a note from the publisher stating that the claims expressed in the article are solely those of the authors and do not necessarily represent the views of their affiliated organizations or the publisher. [Extracted from the article]

Steroid-responsive meningitis-arteritis (SRMA) is a predominantly Th-2 immune-mediated disease, but the exact pathomechanism remains unclear. Interleukin-31 (IL-31) is predominantly produced by T cells with a Th-2 phenotype during proinflammatory conditions. We hypothesize that IL-31 might be involved in the pathogenesis of SRMA. IL-31 was measured in archived samples (49 serum and 52 CSF samples) of dogs with SRMA, meningoencephalitis of unknown origin (MUO), infectious meningoencephalitis, and atopic dermatitis, and of healthy control dogs using a competitive canine IL-31 ELISA. The mean serum IL-31 level in dogs with SRMA (n = 18) was mildly higher compared to dogs with atopic dermatitis (n = 3, p = 0.8135) and MUO (n = 15, p = 0.7618) and markedly higher than in healthy controls (n = 10, p = 0.1327) and dogs with infectious meningoencephalitis (n = 3, no statistics). Dogs with SRMA in the acute stage of the disease and without any pre-treatment had the highest IL-31 levels. The mean CSF IL-31 value for dogs with SRMA (n = 23) was quite similar to that for healthy controls (n = 8, p = 0.4454) and did not differ markedly from dogs with MUO (n = 19, p = 0.8724) and infectious meningoencephalitis. Based on this study, an involvement of IL-31 in the pathogenesis of the systemic Th-2 immune-mediated immune response in SRMA can be assumed as a further component leading to an aberrant immune reaction.

An 8-year-old, castrated male Shih-tzu dog (Case 1) showing ataxia and gait disorder was referred for neurological examination and magnetic resonance imaging. Through comprehensive examinations, the patient was tentatively diagnosed with meningoencephalitis of unknown origin (MUO) and treatment with prednisolone and cytosine arabinoside was started. The symptoms were improving with immunosuppressive treatment. However, severe bacterial cystitis occurred and we could not avoid tapering off prednisolone. Then, neurological signs recurred. Therefore, we added crisdesalazine, which allowed us to reduce the daily dosage of immunosuppressants easily. In another case, a 4-year-old, spayed female Yorkshire terrier dog (Case 2) was referred to our hospital showing a head tilt, circling, and loss of the menace reflex. The patient was tentatively diagnosed with MUO and treatment with some immunosuppressants was attempted. The clinical symptoms improved, but the alleviation was inadequate. Thus, we added crisdesalazine. The neurological signs then markedly improved. Moreover, the drugs could be tapered off more easily than before. Crisdesalazine is a novel drug that has antioxidant and anti-inflammatory action in brain disease and is used particularly for dementia. In this paper, we tried an off-label use of this drug in canine MUO patients, and found that it had, in these two patients, additional therapeutic effects on the MUO.

Introduction: The current prevalence of the metabolically healthy obesity is about 3%. Genetic and nutrition are influencers of such phenotypes. The main goal of this study was to assess the interaction between Dietary Total Antioxidant Capacity (DTAC) and the genotypes of MC4R and Insulin resistance in metabolically healthy/unhealthy overweight and obese women in Iran. Material And Methods: This cross-sectional study was conducted on 237 overweight-obese women with a mean age of 36. The value of Dietary total antioxidant capacity (DTAC) was calculated using the following indices: Total reactive antioxidant potential (TRAP), Trolox equivalent antioxidant capacity (TEAC), and ferric reducing ability of plasma (FRAP). The Metabolic health status was evaluated using the Karelis criteria. Melanocortin 4 receptor single nucleotide polymorphisms were determined by the restriction fragment length polymorphism (PCR-RFLP) method. Also, insulin resistance was evaluated through homeostasis model assessment (HOMA). Result: Our data noted that 72.96% of participants presented Unhealthy Metabolically and 26.94% Healthy Metabolically including 33.5% of the total had T/T genotype, 23.8% had the C/T genotype, and 42.5% had the C/C genotype (P =.05). A linear regression model test showed that the probability of metabolically healthy obesity was significantly higher in patients with the T/C genotype. The test value was statistically significant (95% CI: 0.000-0.001; P =.056, β = 0). No statistically significant relation was observed between study parameters and DTAC values. HOMA-Index was higher in all unhealthy subjects significantly. Conclusions: The findings indicated that there are significant associations between genotypes of rs1333048 SNP and DTAC. The C/C genotype subjects with higher DTAC had a better lipid profile and were metabolically healthier. [ABSTRACT FROM AUTHOR]

Abstract Background Neurofilament light chain (NfL) is a neuron‐specific cytoskeletal protein expressed in axons. Damaged axons of the central nervous system release NfLs into the cerebrospinal fluid (CSF) and the blood. In humans with neurologic diseases, NfL is used as a biomarker. Objectives To identify the potential of NfL as a supportive tool for the diagnosis, prognosis, and monitoring of meningoencephalitis of unknown etiology (MUE) in dogs. Animals Twenty‐six client‐owned healthy dogs, 10 normal Beagle dogs, and 38 client‐owned MUE dogs. Methods Cohort study. The concentrations of NfL in serum and CSF were measured using single‐molecule array technology. Results Median NfL concentration was significantly higher in MUE dogs (serum, 125 pg/mL; CSF, 14 700 pg/mL) than in healthy dogs (serum, 11.8 pg/mL, P

Background & aimsThe factors that distinguish metabolically healthy obesity from metabolically unhealthy obesity are not well understood. Diet has been implicated as a determinant of the unhealthy obesity phenotype, but which aspects of the diet induce dysmetabolism are unknown. The goal of this study was to investigate whether specific macronutrients or macronutrient combinations provoke dysmetabolism in the context of isocaloric, high-energy diets.MethodsMice were fed 4 high-energy diets identical in calorie and nutrient content but different in nutrient composition for 3 weeks to 6 months. The test diets contained 42% carbohydrate (sucrose or starch) and 42% fat (oleate or palmitate). Weight and glucose tolerance were monitored; blood and tissues were collected for histology, gene expression, and immunophenotyping.ResultsMice gained weight on all 4 test diets but differed significantly in other metabolic outcomes. Animals fed the starch-oleate diet developed more severe hepatic steatosis than those on other formulas. Stable isotope incorporation showed that the excess hepatic steatosis in starch-oleate-fed mice derived from exaggerated adipose tissue lipolysis. In these mice, adipose tissue lipolysis coincided with adipocyte necrosis and inflammation. Notably, the liver and adipose tissue abnormalities provoked by starch-oleate feeding were reproduced when mice were fed a mixed-nutrient Western diet with 42% carbohydrate and 42% fat.ConclusionsThe macronutrient composition of the diet exerts a significant influence on metabolic outcome, independent of calories and nutrient proportions. Starch-oleate appears to cause hepatic steatosis by inducing progressive adipose tissue injury. Starch-oleate phenocopies the effect of a Western diet; consequently, it may provide clues to the mechanism whereby specific nutrients cause metabolically unhealthy obesity.

Background: The current study aimed to screen for relationships and different potential metabolic biomarkers involved between metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) in adolescents. Methods: The study included 148 obese adolescents aged between 14 and 16. The study participants were divided into MUO and MHO groups based on the age-specific adolescent metabolic syndrome (MetS) criteria of the International Diabetes Federation. The current study was conducted to investigate the clinical and metabolic differences between the MHO and MUO groups. Multivariate analyses were conducted to investigate the metabolites as independent predictors for the odds ratio and the presence of the MetS. Results: There were significant differences in the three acylcarnitines, five amino acids, glutamine/glutamate ratio, three biogenic amines, two glycerophospholipids, and the triglyceride-glucose index between the MUO group and those in the MHO group. Moreover, several metabolites were associated with the prevalence of MUO. Additionally, several metabolites were inversely correlated with MHO in the MUO group. Conclusions: In this study, the biomarkers found in this study have the potential to reflect the clinical outcomes of the MUO group. These biomarkers will lead to a better understanding of MetS in obese adolescents.

Background: Although, vestibular syndrome is a common neurological presentation, little is known about the diagnostic value of cerebrospinal fluid (CSF) analysis in vestibular syndrome in dogs. Methods: Medical records were retrospectively reviewed, and dogs with vestibular disease that had undergone magnetic resonance imaging of the head, CSF analysis and were diagnosed with central or peripheral vestibular syndrome were included. Disorders affecting the central vestibular system included meningoencephalitis of unknown origin (MUO), brain neoplasia, ischaemic infarct, intracranial empyema or metronidazole toxicity. Disorders affecting the peripheral vestibular system included idiopathic vestibular disease, otitis media/interna or neoplasia affecting the inner ear structures. Total nucleated cell concentration (TNCC), total protein concentration (TP) and cytologic assessment were recorded. Results: A total of 102 dogs met the inclusion criteria. The sensitivity and specificity of increased CSF TNCC to differentiate central from peripheral vestibular syndrome was 49% and 90%, while the sensitivity and specificity of increased TP was 58% and 39%, respectively. The TNCC and TP in dogs with MUO were significantly higher than in dogs with idiopathic vestibular disease (p = 0.000 and p = 0.004). MUO was associated with lymphocytic pleocytosis, while idiopathic vestibular disease and ischaemic infarct were associated with the presence of activated macrophages or normal cytology (p = 0.000). Conclusion: Although consistent CSF abnormalities were observed in dogs with MUO, CSF analysis did not allow reliable differentiation between central and peripheral vestibular syndrome. CSF analysis is not reliable as the sole diagnostic technique in dogs with vestibular disease. [ABSTRACT FROM AUTHOR]

The prevalence of nonalcoholic fatty liver disease (NAFLD) is continuing to rise in many countries, paralleling the epidemic of obesity worldwide. In the last years, the concept of metabolically healthy obesity [MHO, generally defined as obesity without metabolic syndrome (MetS)] has raised considerable scientific interest. MHO is a complex phenotype with risks intermediate between metabolically healthy individuals with normal-weight (NWMH) and patients who are obese and metabolically unhealthy (MUO, i.e. obesity with MetS). In this review we aimed to examine the association and pathophysiological link of NAFLD with MHO and MUO. Compared to NWMH individuals, patients with obesity, regardless of the presence of MetS features, are at higher risk of all-cause mortality and cardiovascular events. Moreover, MHO patients have a greater risk of NAFLD development and progression compared to NWMH individuals. However, this risk is generally lower than that of MUO patients, suggesting a stronger adverse effect of coexisting MetS disorders than obesity per se on the severity of NAFLD. Nevertheless, since MHO is a dynamic state (with a significant proportion of MHO subjects progressing to MUO over time) and NAFLD itself may predict the transition from MHO to MUO, we believe that any effort should be made to identify NAFLD in all obese individuals, although they appear to be “metabolically healthy”. Future research is needed to better understand the role of NAFLD and other pathogenic factors potentially involved in the transition from MHO to MUO and to elucidate how this transition may affect the presence and severity of NAFLD.

Abstract Non-infectious inflammatory (NII) central nervous system (CNS) conditions are primarily diagnosed by the demonstration of inflammatory changes in the cerebrospinal fluid (CSF). However, less-invasive methods and peripheral biomarkers are desired. Changes in circulating microRNA (miRNA), which are short non-coding regulatory RNAs, may serve as biomarkers of disease. The aim of this pilot study was to investigate selected miRNAs in serum and CSF, hypothesizing that the levels of specific miRNAs in serum correlate with their presence in CSF, and that changes in serum miRNAs levels may reflect CNS disease. We profiled serum and CSF samples using quantitative real-time PCR (qPCR) searching for selected and previously profiled miRNAs in serum (let-7a, let-7c, miR-15b, miR-16, miR-21, miR-23a, miR-24, miR-26a, miR-146a, miR-155, miR-181c and miR-221-3p) and in CSF (let-7c, miR-16, miR-21, miR-24, miR-146a, miR-155, miR-181c and miR-221-3p) from 13 dogs with NII CNS disease and six control dogs. We demonstrated the presence of several miRNAs in CSF (let-7c and miR-21 dominating) and serum (miR-23a and miR-21 dominating). However, we generally failed to reproduce consistent results in CSF samples due to several reasons: unacceptable PCR efficiency, a wide variation between cDNA replicates and/or no-amplification in qPCR suggesting very low levels of the investigated miRNAs in canine CSF. Serum samples performed better, and 10 miRNAs qPCR assays were qualified for analysis. We were nevertheless unable to detect a difference in the expression of miRNA levels between cases and controls. Moreover, we could not confirm the results of recent miRNA investigations of canine CNS diseases. We believe that these disagreements highlight the significant effect of methodological/analytical variation, rather than the incapacity of circulating miRNAs as biomarkers of CNS disease. A secondary aim was therefore to communicate methodological challenges in our study and to suggest recommendations for circulating miRNA profiling, including pre-, post- and analytical methods based on our experience, in order to reach reproducible and comparable results in veterinary miRNA research.

This study investigates sex differences in the effects of macronutrient quantity, quality, and timing on mortality in metabolically unhealthy overweight/obesity (MUO) populations. The study included 18,345 participants, including 9204 men and 9141 women. The Cox proportional risk model and isocaloric substitution effects were used to examine the association of macronutrient intake and subtype with all-cause mortality in the MUO populations. After adjusting for the potential covariates, The risk of all-cause mortality was elevated in men in the highest 25% percentile of poor-quality carbohydrates compared with men in the lowest quartile (odds ratio [OR]: 2.04; 95% confidence interval [CI], 1.40-2.98). Compared with women in the lowest quartile, the risk of all-cause mortality for women in the highest 25% percentile for high-quality carbohydrates (OR: 0.74; 95% CI, 0.55-0.99) and unsaturated fatty acids (OR: 0.54; 95% CI, 0.32-0.93) were decreased. In women, replacing low-quality carbohydrates with high-quality carbohydrates on an isocaloric basis reduces the risk of all-cause mortality by approximately 9%. We find that different macronutrient consumption subtypes are associated with all-cause mortality in MUO populations, with differential effects between men and women, and that the risk of all-cause mortality is influenced by macronutrient quality and meal timing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cytosine arabinoside (CA) is a commonly used treatment for dogs with meningoencephalomyelitis of unknown aetiology (MUE) with various proposed protocols, many requiring 24 hours (h) of hospitalization or two visits within 24 h. This is a unidirectional study evaluating the pharmacokinetics of a CA subcutaneous (SC) protocol and a standard constant rate infusion (CRI) protocol in 8 dogs with MUE. Dogs received the CRI (200 mg/m2 IV over 24 h), followed by a SC protocol (50 mg/m2 every 2 h for 4 treatments) four weeks later. Plasma CA concentrations were measured by high‐pressure liquid chromatography–tandem mass spectrometry (HPLC‐MS). Median peak CA concentration for the SC protocol (3.40 µg/ml, range 1.60–9.70 µg/ml) was significantly higher than the CRI (1.09 µg/ml, range 0.77–1.67 µg/ml; p =.02). Median concentration at 1h and 8h following initiation of treatment was significantly higher for the SC protocol (CA1 2.28 µg/ml, range 0.97–2.67; CA8 1.83 µg/ml, range 0.77–2.84) compared to the CRI (CA1 0.01 µg/ml, range 0–0.45; CA8 0.74 µg/ml, range 0.67–1.11; p =.01). While the PK properties of CA when administered as a CRI has been previously investigated, this study demonstrated that CA when administered via repeated 50 mg/m2 injections every 2 h over an 8‐h period, provided sustained plasma levels above its therapeutic target and for a significantly longer duration of time than did a standard CRI protocol. [ABSTRACT FROM AUTHOR]

Background: Neurofilament light chain (NfL) is a neuron‐specific cytoskeletal protein expressed in axons. Damaged axons of the central nervous system release NfLs into the cerebrospinal fluid (CSF) and the blood. In humans with neurologic diseases, NfL is used as a biomarker. Objectives: To identify the potential of NfL as a supportive tool for the diagnosis, prognosis, and monitoring of meningoencephalitis of unknown etiology (MUE) in dogs. Animals: Twenty‐six client‐owned healthy dogs, 10 normal Beagle dogs, and 38 client‐owned MUE dogs. Methods: Cohort study. The concentrations of NfL in serum and CSF were measured using single‐molecule array technology. Results: Median NfL concentration was significantly higher in MUE dogs (serum, 125 pg/mL; CSF, 14 700 pg/mL) than in healthy dogs (serum, 11.8 pg/mL, P <.0001; CSF, 1410 pg/mL, P =.0002). The areas under the receiver operating characteristic curves of serum and CSF NfL concentrations were 0.99 and 0.95, respectively. The cut‐off values were 41.5 pg/mL (serum) and 4005 pg/mL (CSF) for differentiating between healthy and MUE dogs, with sensitivities of 89.19% and 90%, respectively, and specificities of 96.97% and 100%, respectively. The NfL concentration showed a significant decrease (pretreatment, 122 pg/mL; posttreatment, 36.6 pg/mL; P =.02) in the good treatment‐response group and a significant increase (pretreatment, 292.5 pg/mL; posttreatment, 1880 pg/mL, P =.03) in the poor treatment‐response group. Conclusions and Clinical importance: Neurofilament light chain is a potential biomarker for diagnosing MUE and evaluating response to treatment. [ABSTRACT FROM AUTHOR]

A bilateral cranial polyneuropathy was the primary magnetic resonance imaging (MRI) finding in three medium to large breed dogs diagnosed with meningoencephalomyelitis of unknown etiology. All three dogs presented with a progressive history of vestibular ataxia with either central vestibular or multifocal central nervous system (CNS) neuroanatomical localization. Brain MRI revealed variable degree of bilateral enlargement and/or increased contrast enhancement of the optic, oculomotor, trigeminal, facial, and vestibulocochlear nerves, as well as enhancement of the orbital fissure (oculomotor, trochlear, ophthalmic branch of trigeminal, and abducens nerves). There was evidence of intracranial and cranial cervical meningeal contrast enhancement in all three dogs and of cervical spinal cord lesions in 2. In all cases, more cranial nerves were affected than indicated by neurological examination. Cerebrospinal fluid (CSF) analysis was consistent with a mononuclear pleocytosis in 2 cases and a mixed cell (predominantly lymphocytic) pleocytosis in 1 case. All dogs were treated with immune suppressing medications and showed clinical improvement, although some cranial nerve deficits were persistent at follow up 2 months later. These are the first known cases of MUE diagnosed ante-mortem in a canine population documenting bilaterally symmetrical lesions affecting multiple cranial nerves. While MUE is a common cause of non-infectious inflammatory disease in dogs, it likely encompasses more classifications than have previously been reported, and should remain a differential for dogs of all ages and sizes presenting with cranial nerve deficits.

Optic neuritis (ON) is a recognized condition, yet factors influencing recovery of vision are currently unknown. The purpose of this study was to identify prognostic factors for recovery of vision in canine ON of unknown etiology. Clinical databases of three referral hospitals were searched for dogs with presumptive ON based on clinicopathologic, MRI/CT, and fundoscopic findings. Twenty-six dogs diagnosed with presumptive ON of unknown etiology, isolated (I-ON) and MUE-associated (MUE-ON), were included in the study. Their medical records were reviewed retrospectively, and the association of complete recovery of vision with signalment, clinicopathologic findings, and treatment was investigated. Datasets were tested for normality using the D'Agostino and Shapiro-Wilk tests. Individual datasets were compared using the Chi-squared test, Fisher's exact test, and the Mann-Whitney U-test. For multiple comparisons with parametric datasets, the one-way analysis of variance (ANOVA) was performed, and for non-parametric datasets, the Kruskal-Wallis test was performed to test for independence. For all data, averages are expressed as median with interquartile range and significance set at p < 0.05. Twenty-six dogs met the inclusion criteria. Median follow-up was 230 days (range 21–1901 days, mean 496 days). Six dogs (23%) achieved complete recovery and 20 dogs (77%) incomplete or no recovery of vision. The presence of a reactive pupillary light reflex (p = 0.013), the absence of fundoscopic lesions (p = 0.0006), a younger age (p = 0.038), and a lower cerebrospinal fluid (CSF) total nucleated cell count (TNCC) (p = 0.022) were statistically associated with complete recovery of vision. Dogs with I-ON were significantly younger (p = 0.046) and had lower CSF TNCC (p = 0.030) compared to the MUE-ON group. This study identified prognostic factors that may influence complete recovery of vision in dogs with ON. A larger cohort of dogs is required to determine whether these findings are robust and whether additional parameters aid accurate prognosis for recovery of vision in canine ON.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is continuing to rise in many countries, paralleling the epidemic of obesity worldwide. In the last years, the concept of metabolically healthy obesity [MHO, generally defined as obesity without metabolic syndrome (MetS)] has raised considerable scientific interest. MHO is a complex phenotype with risks intermediate between metabolically healthy individuals with normal-weight (NWMH) and patients who are obese and metabolically unhealthy (MUO, i.e. obesity with MetS). In this review we aimed to examine the association and pathophysiological link of NAFLD with MHO and MUO. Compared to NWMH individuals, patients with obesity, regardless of the presence of MetS features, are at higher risk of all-cause mortality and cardiovascular events. Moreover, MHO patients have a greater risk of NAFLD development and progression compared to NWMH individuals. However, this risk is generally lower than that of MUO patients, suggesting a stronger adverse effect of coexisting MetS disorders than obesity per se on the severity of NAFLD. Nevertheless, since MHO is a dynamic state (with a significant proportion of MHO subjects progressing to MUO over time) and NAFLD itself may predict the transition from MHO to MUO, we believe that any effort should be made to identify NAFLD in all obese individuals, although they appear to be "metabolically healthy". Future research is needed to better understand the role of NAFLD and other pathogenic factors potentially involved in the transition from MHO to MUO and to elucidate how this transition may affect the presence and severity of NAFLD. [ABSTRACT FROM AUTHOR]

The UK National Health Service has well-developed site-specific referral pathways for patients with suspected cancer, but historically there has been inequality of access for patients with suspected Metastatic malignant disease of Unknown primary Origin (MUO). The Brighton cancer of unknown primary (CUP) clinic covers a population of about 650 000. As well as 'in-house' referrals, direct general practitioner referrals are also accepted (since 2015), aiming to shorten the diagnostic pathway and improve patient support. We present data from the first 3 years of activity. Referrals were screened by an oncologist, ensuring adherence to the strict referral criterion of imaging evidence of a suspected diagnosis of MUO. A standardised data collection form was completed at each clinic appointment by the CUP team. Outcomes were cross-checked against clinic lists, letters and multidisciplinary meeting (MDM) records. A data analysis was carried out of all referrals to the CUP clinic (2015–2018), including general practitioner referrals. In total, 258 patients were seen in the CUP clinic in the first 3 years. The median age was 71 years (range 23–95 years). Source of referral: general practitioner (30%); physician (27%); acute oncology (24%); other MDM (16%); surgeon (3%). A final diagnosis of cancer was made in 83% of referrals, with a primary site identified in 83% of those cancer cases: 19% haematological, 11% lung, 9% urological, 8% upper gastrointestinal, 6% breast, 5% skin, 4% gynaecological, 4% lower gastrointestinal, 0.3% thyroid and 0.3% sarcoma. 10% of referrals remained with a MUO diagnosis (not fit for further investigation) and 7% had confirmed CUP. 17% had a benign diagnosis (of which 56% were general practitioner referrals). Of the general practitioner referrals: 55% were seen in the CUP clinic, 31% did not meet referral criteria and 14% were declined after MDM review of imaging confirmed benign appearances. The development of direct general practitioner referrals to CUP clinics nationally should be encouraged (as supported by the National Institute for Health and Care Excellence) – they are feasible and manageable within a tertiary CUP clinic, resulting in high rates of cancer diagnoses, with attendant early support from specialist nursing teams and oncological review. • Historically there has been inequality of access for patients with suspected MUO. • Direct GP referrals are feasible and manageable within a tertiary CUP clinic. • MUO patients benefit from early specialist nurse support and oncologist input. [ABSTRACT FROM AUTHOR]

PICO questionIn treatment of canine patients with meningoencephalitis of unknown origin (MUO), is combination therapy of cytosine arabinoside (CA) with prednisolone more effective than prednisolone as a sole therapy at increasing survival time?Clinical bottom lineBased on current available evidence, cytosine arabinoside with prednisolone has greater median survival time than prednisolone as a sole therapy in dogs with meningoencephalitis of unknown origin. The evidence to support this is very weak, as there are currently a low number of published papers with a relatively small number of cases reported in these studies evaluating cytosine arabinoside with prednisolone or prednisolone as a sole therapy for treatment of meningoencephalitis of unknown origin.

Introduction: A variety of treatment options have been described for canine meningoencephalitis of unknown origin (MUO). Few studies focused on radiation therapy as a second line immunomodulating treatment, implicating its effective use. However, a standard radiation therapy protocol is lacking, and further research will help to evaluate the effect of different dose regimens., Methods: Ten dogs diagnosed with MUO based on MRI and CSF findings were prospectively enrolled. The dogs were treated with a shortened whole brain radiation therapy protocol (5 × 4 Gy) in combination with prednisolone. Neurologic changes were quantified using an established scoring scheme. Follow-up MRI and CSF examination was scheduled three months after radiation therapy. Overall survival and time to progression were calculated. Histopathology of the brain was performed in case of death., Results: Seven dogs were diagnosed de novo and three had a history of relapsing MUO. Neurological status improved in all 10 dogs during radiation therapy, with 4/10 returning to normal shortly after radiation therapy. Three dogs died within the first three months after radiation therapy. At follow-up MRI lesions completely resolved in two dogs, partially resolved in five dogs, and progressed in one dog. After follow-up MRI, dogs were further treated with prednisolone monotherapy (two dogs) and additional immunosuppressant drugs (five dogs). Overall, four dogs showed disease progression, with a mean time to progression of 691 days (95%CI: 396-987) and mean overall survival for all dogs was 723 days (95%CI: 436-1011) (both medians not reached). Histopathology confirmed MUO in three dogs but was suggestive for oligodendroglioma in one dog. Radiation induced side effects were not seen., Conclusion: Shortened whole-brain radiation therapy could be an additional treatment option for MUO in conjunction to prednisolone, specifically for cases that require rapid relief of symptoms and with relapsing history., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Herzig, Beckmann, Körner, Steffen and Rohrer Bley.)

Although long-term outcomes of meningoencephalitis of unknown aetiology (MUA) in dogs have been evaluated, little is known about short-term survival and initial response to therapy. The aim of this study was to evaluate possible prognostic factors for 7-day survival after diagnosis of MUA in dogs. Medical records were reviewed for dogs diagnosed with MUA between 2006 and 2015. Previously described inclusion criteria were used, as well as 7-day survival data for all dogs. A poor outcome was defined as death within 1 week. Of 116 dogs that met inclusion criteria, 30 (26%) died within 7 days of diagnosis. Assessed variables included age, sex, bodyweight, duration of clinical signs and treatment prior to diagnosis, venous blood glucose and lactate levels, white blood cell count on complete blood count, total nucleated cell count/total protein concentration/white blood cell differentiation on cerebrospinal fluid (CSF) analysis, presence of seizures and cluster seizures, mentation at presentation, neuroanatomical localisation, imaging findings and treatment after diagnosis. Multivariate analysis identified three variables significantly associated with poor outcome; decreased mentation at presentation, presence of seizures, and increased percentage of neutrophils on CSF analysis. Despite initiation of appropriate treatment, more than a quarter of dogs died within 1 week of diagnosis of MUA, emphasising the need for evaluation of short-term prognostic factors. Information from this study could aid clinical staff to provide owners of affected dogs with prognostic information. [ABSTRACT FROM AUTHOR]