Web-Vet TM Neurology Specialists
Meningitis / Encephalitis
Encephalitis and meningitis often exist concurrently (meningoencephalitis) in dogs and cats. Numerous infectious and non-infectious aetiologies exist. The incidence of infectious agents causing meningoencephalitis varies with geographic location
MUO
This 2019 review provides a comprehensive overview of recent developments in the clinical presentation, diagnostic findings, possible prognostic factors, treatment and outcome in dogs diagnosed with MUO.
This case series is the first report describing both clinical and histopathological findings of feline MUO: Four cats (age: 1.7–17.8 years) showed acute to chronic progressive neurological signs of encephalopathy or myelopathy. Three cats had extraneural signs (hyperthermia, weight loss, hyporexia, leukocytosis). Magnetic resonance imaging (MRI) showed multifocal intraparenchymal lesions in forebrain, brainstem or spinal cord with homogenous contrast enhancement (2/2). Cerebrospinal fluid (CSF) examination was normal or displayed albuminocytologic dissociation. Histopathology revealed a multifocal, lympho-histiocytic meningoencephalitis in three cases and a lympho-histiocytic myelitis in one case.
Feline meningoencephalomyelitis of unknown origin: A retrospective analysis of 16 cases
This study aimed to describe the signalment, clinical signs, magnetic resonance imaging (MRI) findings, cerebrospinal fluid (CSF) analysis, treatment, and outcome of feline meningoencephalomyelitis of unknown origin (FMUO).
Median age was 9.4 years. Clinical signs included ataxia, proprioceptive deficits, seizures, and spinal hyperesthesia. The CSF nucleated cell count was increased (median 70.7 cells/μL), with predominantly mixed pleocytosis and CSF protein concentration was increased in 15/16 cats. Magnetic resonance imaging showed intraparenchymal infiltrative ill-defined lesions in 13 cases. All cats received a corticosteroid-based treatment protocol; additional therapies included lomustine, cytarabine, and anticonvulsant medications. Mild neurological signs were recorded in 5/12 cats but 7/12 cats were neurologically normal at re-examination.
This study aims to compare the differences in survival and clinical response of MUE according to the adjuvant immunosuppressant use. Medical records of 82 dogs diagnosed with MUE were reviewed retrospectively.
The overall survival time was 769 days (range 14–2687 days). The median survival time for each adjunctive was: leflunomide 1035 days (range 126–2163 days), mycophenolate mofetil 865 days (range 39–2191 days), cyclosporin 441 days (range 11–2176 days), cytosine arabinoside 754 days (range 6–1898 days) and a combination of mycophenolate mofetil and cytosine arabinoside 132 days (range 23–1227 days). There was no significant difference in the incidence rate of adverse events according to the immunosuppressants, but moderate to severe anemia was confirmed in 3 patients (18.7%) in the leflunomide group.
This retrospective study of 447 dogs with MUO aimed to identify prognostic variables.
Nearly two-thirds of the dogs were still alive at 6 months and nearly 50% of dogs followed up had a relapse with a median time to onset of 7 months. Negative associations for survival to 6 months included dog breed (Pugs), the presence of seizure activity, weakness, and a high overall neurological disability score. Incomplete resolution of neurological signs was seen in 36% of survivors and this was associated with a relapse at a future date.
The aim of this study was to evaluate the prognostic value of different MRI variables for predicting survival at 12 months and long-term relapse.
This was a retrospective study of 138 dogs which 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 was associated with longer survival and higher T1 post-contrast lesion load was associated with relapse.
The aim of this study was to describe the long-term outcomes, overall survival, progression-free survival, and prognostic factors in 37 dogs with presumed necrotizing encephalitis (NE) based on MRI and CSF diagnosis.
The medians of the overall and progression-free survival times were 639 days and 233 days, respectively. Overall survival was highly correlated with progression-free survival. Four dogs (11%) died or were euthanized within 3 months of diagnosis. Relapse within 6 months was associated with a shorter overall survival. However, no prognostic factors for overall survival were found. The category of patients with presenting clinical signs that lasted 29 days to 6 months was associated with a higher risk of relapse. Seizures were presented in 75.7% of dogs, with a recurrence rate of 100%.
This article reviews the current evidence for the different strategies for the management of meningoencephalitis of unknown origin in dogs (MUO). While the most commonly reported immunosuppressive combinations from the literature are corticosteroids combined with either cytarabine or cyclosporine, the decision on when and how quickly to taper this treatment is very much clinician-dependent as a best practice has not been established but also often dependent on the patient's response or lack of it.
The aim of this study was to compare neurological deterioration rates at 7 days between dogs with MUO treated with corticosteroids alone or combined with cytosine arabinoside (CA) continuous rate infusion (CRI) and compare clinical deterioration and survival at 30 and 100 days. Sixty‐nine dogs with magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) features or both compatible with MUO.
Thirty‐five dogs were allocated to corticosteroid only, and 34 dogs were allocated to combined CA CRI and corticosteroid. Proportions failing treatment at 7, 30, and 100 days were 7/35 (20%), 9/35 (26%), and 15/35 (43%) in the corticosteroid‐only group and 8/34 (24%), 11/34 (32%), and 23/34 (68%) in the corticosteroid and CA CRI group. All‐cause mortality at 100 days was not significantly different between groups. Clinically relevant treatment‐related adverse effects were not observed. Interestingly this study found no difference in outcome between corticosteroid monotherapy and combined cytarabine CRI and corticosteroid therapy in dogs with MUO.
This study reviews outcomes in 671 dogs treated with various combinations of glucocorticoids (GCs) and immunosuppressive drugs and reported since 2009, aiming to determine whether recommendations can be drawn from the material published during more recent decades.
One of the findings suggests that the use of glucocorticoids as a single therapy is associated with survival periods of similar magnitude to dogs receiving glucocorticoids plus an adjunctive therapy and with extremely wide ranges, although direct comparison between studies is difficult. Despite the use of a wide range of different immunosuppressive agents there is still not reliable evidence that any of these are superior to GCs alone and there are potential benefits to owners to relying upon GCs alone, such as the ease of access, cheap cost and ease of administration. Nevertheless, this must also be balanced against the high rate of adverse effects of high-dose GC administration.
Whole Brain Radiation Therapy for MUO in Dogs
The use of radiation therapy (RT) in conjunction with glucocorticoid treatment for MUO was first reported in 1989 and subsequently in 2 other studies. However, no standard RT protocol has so far been established. In a study published in Frontiers, the authors (from the Dept. for Small Animals, Vetsuisse Faculty, University of Zurich) propose a shortened whole-brain RT protocol and propose it as a fast, additional treatment option in conjunction with glucocorticoid treatment without other safety issues. With that in mind, the authors suggest that this RT protocol could be considered in dogs being refractory to medical treatment alone or suffering from severe medical side effects.
This case series documents 3 dogs with bilateral cranial polyneuropathy noted on magnetic resonance imaging (MRI). 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.
This study aimed to evaluate the association between DLA class II genes and MUO development in Chihuahuas. Blood samples were obtained from 22 Chihuahuas with MUO (MUO group) and 46 without neurological diseases (control). The allele sequences of three DLA class II loci were determined, and haplotypes were estimated from these data. In total, 23 haplotypes were detected. The frequency of one haplotype (DLA-DRB1*015:01--DQA1*006:01--DQB1*023:01) was significantly higher in the MUO group than in the control group. The results suggest that the development of MUO in Chihuahuas may be associated with DLA class II genes. Because the identified risk haplotypes differed from those of other breeds, the pathogenesis of NIME-related diseases may differ among dog breeds.
The aim of this study was to investigate 16 Pug dogs at genetic risk for NME to see if they manifest neurological abnormalities before developing pathognomonic clinical signs of NME.
The study looked at 36 pug dogs less than 4 years of age asymptomatic for NME. Neurological examinations were performed 4 weeks apart to document reproducible findings of central nervous system disease. Magnetic resonance imaging, cerebrospinal fluid analysis, and testing for infectious diseases were performed in all pugs with reproducible abnormalities detected on neurological examination. The overall risk allele frequency in this cohort was 40%; 5 (14%) dogs were high risk, 19 (53%) dogs were medium risk, and 12 (33%) dogs were low genetic risk for NME. Reproducible abnormalities detected on neurological examination were identified in 8/24 (33%) genetically at‐risk dogs and 0/12 (0%) low risk dogs. Clinical abnormalities included multifocal spinal pain in 8/8, reduced menace response in 5/8, and lateralizing postural reaction deficits in 5/8 pugs. There was a strong association between genotype risk and the presence of this clinical phenotype
Canine CNS Infections
Bacterial Meningitis Secondary to Otogenic Infection in French Bulldogs
This retrospective study was published on 10 French bulldogs with bacterial meningitis/encephalitis suspected secondary to otogenic infection. The study suggests that this breed may be at greater risk of developing this condition due to poor auditory tube drainage and underlying dermatological disease.
Of particular interest, analysis of CSF documented pleocytosis in all eight dogs tested and intracellular bacteria were seen in three with positive bacteriological culture in two dogs.
To describe the clinical signs and outcome of 41 dogs presenting with neurological signs secondary to Neospora caninum infection.
Cerebello-vestibular signs predominated; however, presenting clinical signs were varied and the neurolocalisation was often multifocal in nature (46.3%), making neosporosis an important differential diagnosis for meningoencephalitis of unknown origin. Complete clinical improvement was rare (5.6%), and relapses were common (27.8% cases with follow-up).
A retrospective case series on bacterial meningitis and meningoencephalitis in dogs. Of particular interest, only 3 out of these 24 dogs had pyrexia, only 12 dogs had altered mentation and only 10 dogs had cervical hyperesthesia which is in contrast to what is often seen in people. Intracellular bacteria were visualised in 15/24 with positive CSF bacteriology culture in 8/21. None of the blood or urine cultures were positive. Otitis media/interna was the most common source of infection being diagnosed in 15/24 with 12 of them being brachycephalic breeds.
Median duration of antibiotic treatment was 8 weeks (ranging from 2 to 16 weeks). This study did not include dogs with intracranial empyema or abscess formation
Cladophialophora bantiana is a dematiaceous fungus, meaning that it produces a melanin-like pigment within its hyphae or spore walls.
This report documents the magnetic resonance imaging (MRI) and pathological findings and is suggestive of a possible route of infection for central nervous system (CNS) phaeohyphomycosis infections in the dog.
Tick-borne encephalitis (TBE) is a viral disease, endemic in Europe, causing mainly nonspecific febrile illness followed by a remission phase in people. After this initial phase the disease may affect the nervous system in up to 50% of the cases.
The aim of this paper was to characterize the clinical aspects of TBE and to investigate fatality rate, long-term outcome, and the long-term neurological sequelae in 54 dogs infected with TBE.
In 62% of the TBE cases unspecific signs were described before the onset of neurological signs. Case fatality rate was 33% and all dogs died within the first 4 months after diagnosis. Long-term neurological sequalae were detected in 17% of the TBE cases
Neospora tachyzoites are commonly found in striated muscles, particularly in masseter and temporalis muscles with concurrent involvement of the CNS. This study looked at serum activity of CK and AST as a rapid screen for predicting positive serology in dogs with meningoencephalitis caused by Toxoplasma gondii or Neospora caninum compared to dogs with noninfectious meningoencephalitis. Results of this study suggest that high serum CK and AST activity can increase the suspicion for neosporosis while awaiting serological tests for dogs with meningoencephalitis. This clinical decision aid could be particularly useful in cases where urgent treatment is required before serological testing results are available, although study on a larger scale would be required to quantify these findings.
Suspected tick-borne flavivirus meningoencephalomyelitis in dogs from the UK: six cases (2021)
This case series aimed to describe the clinical, clinicopathological, and imaging findings, as well as the outcomes in six dogs with meningoencephalitis and/or meningomyelitis caused by a flavivirus in the UK.
All dogs presented an initial phase of pyrexia and/or lethargy followed by progressive signs of spinal cord and/or intracranial disease. Magnetic resonance imaging showed bilateral and symmetrical lesions affecting the grey matter of the thalamus, pons, medulla oblongata, and thoracic or lumbar intumescences with none or mild parenchymal and meningeal contrast enhancement. Serology for tick-borne encephalitis virus was positive in five dogs with the presence of seroconversion in two dogs. Three dogs survived but presented neurological sequelae. Three dogs were euthanased due to the rapid progression of the clinical signs or static neurological signs.
The first goal of this study was to determine the proportion of dogs where CNS inflammation was caused by an infectious agent versus a probable immune-mediated etiology (i.e., MUO) in Brazil. The secondary goals of this study were to examine and define associations between abnormal CSF and neuroimaging findings, in addition to defining the age and most common neurological clinical signs. Presumptive MUO was observed in 152/168 of the included dogs (90.5%) and infectious ME was identified in 16/168 (9.5%) of dogs. Canine distemper virus (CDV) was the most common cause of infectious ME in 10/16 dogs (62.5%). Of the total cases with a positive infectious disease result, 3/16 (18.7%) had normal CSF results and 13/16 (81.3%) had abnormal CSF results. MRI and CT abnormalities in the brain were detected in 74 and 39% of dogs with inflammatory CSF, respectively. MRI and CT abnormalities in the spinal cord were detected in 90 and 57% of dogs with inflammatory CSF results, respectively. Age was not significantly different between infectious ME and presumptive MUO groups (p = 0.15). Seizures were the most common clinical sign reported for both MUO (36.8% of cases) and infectious ME (31.2% of cases).
Feline CNS Infections
This study describes treatment protocols, response to treatment, and outcomes in 32 cats with FIP treated with a combination of GS-441524 and injectable remdesivir. Study population included cats diagnosed with effusive and non-effusive FIP including those with ocular and neurological involvement. Of interest, cases of neurological and ocular FIP require higher doses of injectable GS-441524 because of poor drug access across the blood-ocular and blood-brain barriers. Cases of neurological FIP or ocular FIP in this study therefore were started on dosages of 15 to 20 mg/kg of remdesivir and PO GS-441524 q24h. Four of 5 cats (80%) that presented with neurological disease and 4 of 6 cats (67%) with ocular involvement recovered fully.
GS-441524 is a parent nucleoside of GS-5734 which has been effective in preventing experimental Ebola in rhesus monkeys. In this study, four cases of naturally occurring FIP with CNS involvement were treated with the antiviral nucleoside analogue GS‐441524 (5‐10 mg/kg) for at least 12 weeks. All cats had a positive response to treatment. Three cats are alive off treatment (528, 516, and 354 days after treatment initiation) with normal physical and neurologic examinations. In 1 case, resolution of disease was defined based on normalization of MRI and CSF findings and resolution of cranial and caudal segment disease with ocular imaging. Treatment with GS‐441524 shows clinical efficacy and may result in clearance and long‐term resolution of neurological FIP. This study hopefully paves the way to the future commercialisation of this antiviral drug against FIP. Please note that GS‐441524 is not readily available for routine clinical use at the moment. For a webinar on this topic, visit our webinar page.
The aim of this study was to review a larger population of cats with intracranial empyema from multiple aetiologies and document their signalment, imaging findings, treatment protocols (including medical and/or surgical management) and to compare outcomes.
Ten cases underwent medical and surgical management combined and 10 underwent solely medical management. Short-term outcome showed that 90% of surgically managed and 80% of medically managed cats were alive at 48 h post-diagnosis. Long-term survival showed that surgically managed cases and medically managed cases had a median survival time of 730 days (range 1–3802 days) and 183 days (range 1–1216 days), respectively. No statistical significance in short- or long-term survival (P >0.05) was found between medically and surgically managed groups.