Corrigendum: Magnetic resonance imaging prognostic factors for survival and relapse in dogs with meningoencephalitis of unknown origin.

[This corrects the article DOI: 10.3389/fvets.2024.1370882.].

Why do some individuals with obesity remain metabolically healthy?

A recent study by Peterson et al. that characterized individuals with metabolically healthy obesity (MHO) or metabolically unhealthy obesity (MUO) in depth provides insights into the potential pathogenesis of MUO that accounts for much of the cardiometabolic disease and excess mortality caused by the obesity epidemic.

Clinical features, treatment, and outcome of juvenile dogs with meningoencephalitis of unknown etiology.

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.

Allele frequency of a genetic risk variant for necrotizing meningoencephalitis in pug dogs from Europe and association with the clinical phenotype.

Introduction: Necrotizing meningoencephalitis (NME) in pugs is a potentially fatal disease, which needs lifelong treatment with immunosuppressive or immunomodulatory drugs and shares parallels with acute fulminating multiple sclerosis. Genetic variants of the DLA class II gene are associated with an increased risk for NME. Genetic testing is recommended prior to breeding. The aim of this study was to describe the current allele frequency of a previously identified NME risk variant in the European pug population. A secondary aim was to investigate the association of the NME risk variant with the clinical phenotype in pugs. Methods: Results of genetic testing for the CFA12:2605517delC variant in European pugs between 2012 and 2020 were retrieved (n = 5,974). A validated questionnaire was mailed to all submitters of samples for further information on neurological signs, diagnostic tests, and disease course. Results: The allele frequency of the CFA12 NME risk variant was 25.7% in the European pug population dogs; 7.4% of the dogs were homozygous and 36.7% were heterozygous for the NME risk variant on CFA12. Completed questionnaires were available in 203 dogs including 25 dogs with epileptic seizures or other neurological signs. The clinical phenotype was consistent with NME in 3.9% with a median age of onset of 1.0 years, and indicative of idiopathic epilepsy in 2.9% with a median onset of 2.5 years. Eleven dogs remained unclassified. Pugs with the NME phenotype were significantly more frequently homozygous for the NME risk variant on CFA12 compared to pugs ≥6 years without neurological signs or seizures (p = 0.008). Discussion: The CFA12:2605517delC genetic risk variant is widely distributed in the European pug population and frequently homozygous in pugs with a NME phenotype. The data support the clinical relevance of the CFA12:2605517delC genetic risk variant.

Magnetic resonance imaging prognostic factors for survival and relapse in dogs with meningoencephalitis of unknown origin.

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.

Prognosis in meningoencephalitis of unknown origin in dogs: Risk factors associated with survival, clinical relapse, and long-term disability.

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.

Case report: Necrotizing leukomyelitis and meningitis in a Pomeranian.

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.

Sex differences in the relationships between macronutrients and all-cause mortality in individuals with metabolically unhealthy overweight/obesity.

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.

Malignant ureteral obstruction: comparison of metallic, 8 French and 6 French ureteric stents after failure of initial ureteric stent.

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.

MHO or MUO? White adipose tissue remodeling.

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.

Differences in metabolic characteristics between Metabolically Healthy Obesity (MHO) and Metabolically Unhealthy Obesity (MUO) in weight reduction therapy.

Metabolically Healthy Obesity (MHO) is generally recognized as the absence of any metabolic disorders and cardiovascular diseases, including type 2 diabetes, dyslipidemia, and hypertension, in obese individuals; however, it is not clearly defined. Therefore, the present study investigated differences in metabolic characteristics between individuals with MHO and Metabolically Unhealthy Obesity (MUO) during weight reduction therapy. The key factors defining MHO and the importance of weight reduction therapy for MHO were also examined. Cohort data from the Japan Obesity and Metabolic Syndrome (JOMS) study were analyzed. Subjects were divided into the MHO (n = 25) and MUO (n = 120) groups. Prior to weight reduction therapy, serum adiponectin levels were significantly higher in the MHO group than in the MUO group. Serum adiponectin levels also negatively correlated with the area of subcutaneous adipose tissue (SAT) and Homeostasis model assessment (HOMA)-R in the MHO group, but not in the MUO group. Collectively, the present results suggest the importance of adiponectin for maintaining metabolic homeostasis in the MHO group. On the other hand, no significant differences were observed in inflammatory markers between the MHO and MUO groups, suggesting the presence of chronic inflammation in both groups. Furthermore, a positive correlation was noted between changes in serum cystatin C levels and waist circumference in the MHO group, which indicated that despite the absence of metabolic disorders, the MHO group exhibited anti-inflammatory responses during weight reduction therapy. These results underscore the significance of weight reduction even for individuals with MHO.

Investigation of side effects to treatment and cause of death in 63 Scandinavian dogs suffering from meningoencephalitis of unknown origin: a retrospective study.

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.

Adherence to the Mediterranean diet as a possible additional tool to be used for screening the metabolically unhealthy obesity (MUO) phenotype.

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.

Elevated Interleukin-31 Levels in Serum, but Not CSF of Dogs with Steroid-Responsive Meningitis-Arteritis Suggest an Involvement in Its Pathogenesis.

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.

Evidence for proton-pump inhibitor (PPI)-associated dysbiosis in metabolically unhealthy obesity.

Obesity adversely impacts millions of American adults by predisposing them to significant health risks and further complications. Obesity is differentiated into two groups: metabolically healthy and metabolically unhealthy. In contrast to metabolically healthy counterparts, obese individuals who are metabolically unhealthy display hallmark symptoms of metabolic syndrome (e.g., hypertension, dyslipidemia, hyperglycemia, abdominal obesity). Gastroesophageal reflux disease (GERD) commonly occurs in all obese populations, as do poor dietary habits. Proton-pump inhibitors (PPIs), due to their wide availability, are most often used to treat GERD-related heartburn and other symptoms. Here, we review the evidence on how poor diet as well as short- and long-term use of PPIs adversely affect the gastrointestinal microbiota to cause dysbiosis. Key components of dysbiosis-induced metabolically unhealthy obesity (MUO) associated with PPI use include "leaky gut," systemic low-grade inflammation, and reduced amounts of short-chain fatty acids (SCFAs) such as butyrate that promote metabolic health. The benefit of using probiotics to mitigate PPI-induced dysbiosis and MUO is also discussed.

Off-Label Use of Crisdesalazine (GedaCure) in Meningoencephalitis in Two Dogs.

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.

Metabolome Profiling and Pathway Analysis in Metabolically Healthy and Unhealthy Obesity among Chinese Adolescents Aged 11-18 Years.

The underlying mechanisms of the development of unhealthy metabolic phenotypes in obese children and adolescents remain unclear. We aimed to screen the metabolomes of individuals with the unhealthy obesity phenotype and identify the potential metabolic pathways that could regulate various metabolic profiles of obesity in Chinese adolescents. A total of 127 adolescents aged 11-18 years old from China were investigated using a cross-sectional study. The participants were classified as having metabolically healthy obesity (MHO) or metabolically unhealthy obesity (MUO) based on the presence/absence of metabolic abnormalities defined by metabolic syndrome (MetS) and body mass index (BMI). Serum-based metabolomic profiling using gas chromatography-mass spectrometry (GC-MS) was undertaken on 67 MHO and 60 MUO individuals. ROC analyses showed that palmitic acid, stearic acid, and phosphate could predict MUO, and that glycolic acid, alanine, 3-hydroxypropionic acid, and 2-hydroxypentanoic acid could predict MHO (all p < 0.05) from selected samples. Five metabolites predicted MUO, 12 metabolites predicted MHO in boys, and only two metabolites predicted MUO in girls. Moreover, several metabolic pathways may be relevant in distinguishing the MHO and MUO groups, including the fatty acid biosynthesis, fatty acid elongation in mitochondria, propanoate metabolism, glyoxylate and dicarboxylate metabolism, and fatty acid metabolism pathways. Similar results were observed for boys except for phenylalanine, tyrosine and tryptophan biosynthesis, which had a high impact [0.098]. The identified metabolites and pathways could be efficacious for investigating the underlying mechanisms of the development of different metabolic phenotypes in obese Chinese adolescents.

Association between neurofilament light chain concentration and lesion size in dogs with meningoencephalitis of unknown origin.

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.

Development of a reliable clinical assessment tool for meningoencephalitis in dogs: The neurodisability scale.

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.

A shortened whole brain radiation therapy protocol for meningoencephalitis of unknown origin in dogs.

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.