CNS disease in the cat: current knowledge of infectious causes

PRACTICAL RELEVANCE: Neurological disease is a relatively common reason for referral, constituting approximately 10% of the feline referral caseload. Nearly one-third to one-half of these cases may be infectious in origin. As such, an awareness of infectious diseases causing central nervous system (CNS) signs in cats, and their clinical diagnosis and management, is relevant to anyone dealing with cats on a regular basis. GLOBAL IMPORTANCE: Some conditions (eg, rabies) are more common in certain countries than others. Conditions such as feline infectious peritonitis (FIP) and toxoplasmosis are of global significance. PATIENT GROUP: Many infectious diseases may affect any feline population. Some, such as FIP, are more common in pedigree households, whereas others such as toxoplasmosis, feline immunodeficiency virus (FIV) or feline leukaemia virus (FeLV) infections, are more likely to affect a single cat with an outdoor lifestyle. EQUIPMENT: All patients benefit from thorough history taking and clinical, neurological and ophthalmic examinations, which all require minimal equipment. Infectious diseases may often be diagnosed on blood samples; however, definitive diagnosis may require more extensive investigation involving cerebrospinal fluid analysis or advanced imaging necessitating access to computed tomography or magnetic resonance imaging. EVIDENCE BASE: The information in this review, which summarises current knowledge of infectious diseases affecting the CNS, is collated from publications on the infectious diseases comprising previous research papers, review articles, case series, case reports and textbooks, supplemented by the clinical experience of the authors.     

Central nervous system relapses in 3 dogs with B-cell lymphoma

This report describes cases of central nervous system (CNS) relapse that occurred during chemotherapy in 3 dogs with lymphoma. Diagnosis was made by a combination of clinical signs and cytology of cerebrospinal fluid. The suspected risk factors, clinical features common to the 3 dogs, and treatment options are discussed.     

Clinical signs, imaging features, neuropathology, and outcome in cats and dogs with central nervous system cryptococcosis from California

Background: Cryptococcus spp. is a fungal pathogen with a predilection for the central nervous system (CNS). Objectives: To compare the clinical, advanced imaging, and neuropathologic findings in dogs and cats with CNS cryptococcosis, and to evaluate outcome of treatment in these animals. Animals: Twenty‐six cats and 21 dogs with CNS cryptococcosis. Methods: Medical records were reviewed for clinical findings and results of CNS imaging. Archived cerebrospinal fluid and CNS tissue specimens were reviewed for pathology. Findings in cats were compared with those in dogs and the effects of variables on survival were determined by survival curve analysis. Results: When present, pain was localized to the cervical region in dogs and was generalized or localized to the thoracolumbar spine or pelvic limbs in cats. Magnetic resonance imaging (MRI) findings were variable but correlated with CNS histopathological findings of meningitis, meningitis with gelatinous pseudocyst formation, and granulomatous mass lesions. Peripherally enhancing brain lesions were seen only in cats. Histopathologically, the inflammatory response was milder in cats compared with dogs. Remissions of ≥1 year occurred in 32% of treated animals. Altered mentation was associated with negative outcome. Glucocorticoid use after diagnosis was associated with improved survival in the first 10 days. Conclusions and Clinical Importance: Lesions seen on MRI reflected neuropathological findings and were similar to those reported in human patients. The immune response to infection may differ between cats and dogs, or relate to the infecting cryptococcal species. Long‐term (>6 month median survival time) survival may be possible in animals surviving ≥4 days after diagnosis.     

Cerebrospinal fluid analysis and magnetic resonance imaging in the diagnosis of neurologic disease in dogs: a retrospective study

BACKGROUND: Diagnosis of central nervous system (CNS) abnormalities in dogs can be challenging antemortem. Historically, cerebrospinal fluid (CSF) analysis has been used for routine diagnostic evaluation of animals with suspected neurologic disease; however, with increasing availability of magnetic resonance (MR) imaging, the need for concurrent CSF analysis may be questioned. OBJECTIVE: The purpose of this study was to retrospectively assess and compare the diagnostic information contributed from MR imaging and CSF analysis in a population of dogs presenting with neurologic disease. METHODS: Results of concurrent MR imaging and CSF analysis were evaluated in dogs presented for neurologic diseases. Based on clinical diagnosis, the sensitivity of CSF analysis and MR imaging for detecting a nervous system abnormality was calculated. Dogs with diagnoses confirmed by other diagnostic modalities were also evaluated separately. RESULTS: A total of 256 dogs were included in the study. For clinical diagnoses in which abnormalities were expected, MR imaging abnormalities were found in 89% and CSF abnormalities in 75% of dogs; CSF abnormalities were more common than MR imaging abnormalities only in inflammatory CNS disease. The majority of CSF abnormalities were nonspecific; an etiologic diagnosis was determined in only 2% of CSF samples. MR imaging excelled in detecting structural disorders, revealing 98% of vertebral abnormalities. In confirmed cases (n = 55), 76% of MR images and 9% of CSF samples were diagnostic. When intervertebral disk disease (IVDD) and vertebral malformation were excluded from analysis (n = 16 remaining), 25% of MR images and 6% of CSF cytology results were highly indicative of the confirmed diagnoses; CSF titer results provided the diagnosis in 25% of these cases. CONCLUSION: CSF analysis may not be necessary when MR findings of IVDD or vertebral malformation/instability are obvious; however, when the cause of neurologic disorder is uncertain, concurrent MR imaging and CSF analysis provides the greatest assistance in establishing a clinical diagnosis.     

Combined cytosine arabinoside and prednisone therapy for meningoencephalitis of unknown aetiology in 10 dogs

OBJECTIVES: The differential diagnosis for young to middle-aged dogs with progressive neurological signs, focal or multifocal computed tomography/magnetic resonance imaging lesions, mononuclear cerebrospinal fluid pleocytosis and negative infectious titres includes granulomatous meningoencephalomyelitis, breed-specific meningoencephalitis, infectious meningoencephalitis of unknown origin and central nervous system neoplasia. The terminology meningoencephalitis of unknown aetiology may be preferable for cases that lack histopathological diagnoses. The safety and efficacy of a combination of cytosine arabinoside and prednisone protocol is evaluated, in this study, for the treatment of meningoencephalitis of unknown aetiology in 10 dogs. METHODS: Cases were selected based on neuroanatomical localisation, negative regional infectious disease titres, cerebrospinal fluid pleocytosis and brain imaging. Clinical response was gauged through follow-up examinations, owner and referring veterinarian surveys and review of medical records. RESULTS: Partial or complete remission was achieved in all dogs; the median survival time for the 10 dogs was 531 days (range 46 to 1025 days), with five of the 10 dogs alive at the time of writing. CLINICAL SIGNIFICANCE: Prednisone/cytosine arabinoside is a safe empirical therapy for dogs with meningoencephalitis of unknown aetiology; this drug combination may prolong survival time.     

Cerebellar cortical degeneration with selective granule cell loss in Bavarian mountain dogs

Three Bavarian mountain dogs aged between 18 and 20 months, not related to each other, were presented with chronic signs of cerebellar dysfunction. On sagittal T2-weighted magnetic resonance imaging brain images, the tentative diagnosis of cerebellar hypoplasia was established based on an enlarged cerebrospinal fluid space around the cerebellum and an increased cerebrospinal fluid signal between the folia. Post-mortem examination was performed in one dog and did show an overall reduction of cerebellar size. On histopathologic examination, a selective loss of cerebellar granule cells with sparing of Purkinje cells was evident. Therefore, the Bavarian mountain dog is a breed where cerebellar cortical degeneration caused by the rather exceptional selective granule cell loss can be seen as cause of chronic, slowly progressive cerebellar dysfunction starting at an age of several months.     

THREE TESLA MAGNETIC RESONANCE IMAGING FINDINGS IN 12 CASES OF CANINE CENTRAL EUROPEAN TICK‐BORNE MENINGOENCEPHALOMYELITIS

Central European tick‐borne encephalomyelitis can be challenging to diagnose in dogs because the virus may not be detected in blood and cerebrospinal fluid (CSF) after the first viremic stage of the disease. The purpose of this retrospective case series study was to describe 3 Tesla magnetic resonance imaging (3T MRI) findings in a sample of dogs with a confirmed diagnosis of tick‐borne encephalomyelitis. Dogs were included if they had neurological signs consistent with tick‐borne encephalomyelitis, history of a stay in endemic areas for tick‐borne encephalomyelitis virus, 3T MRI of the brain and/or spinal cord, cerebrospinal fluid changes compatible with viral infection and positive antibody titers in cerebrospinal fluid or pathologic confirmation of tick‐borne encephalomyelitis. Twelve dogs met inclusion criteria. Ten out of 12 patients had 3T MRI lesions at the time of presentation. One patient had persistent lesions in follow‐up MRI. The 3T MRI findings included bilateral and symmetrical gray matter distributed lesions involving the thalamus, hippocampus, brain stem, basal nuclei, and ventral horn on the spinal cord. All lesions were hyperintense in T2‐weighted sequences compared to white matter, iso‐ to hypointense in T1‐weighted, nonenhancing, and had minimal or no mass effect or perilesional edema. Six patients survived while the remaining six dogs were euthanized. Necropsy revealed neuronophagia and gliosis of the gray matter of the affected regions seen in 3T MRI, in addition to the cerebellum. Findings from the current study indicated that tick‐borne encephalomyelitis should be included in the differential diagnosis list for dogs with the above described 3T MRI characteristics.     

Magnetic resonance imaging,clinicopathologic findings,and clinical progression of a puppy with confirmed Eastern equine encephalitis virus

A 5-month-old puppy was evaluated for rapidly progressive neurologic signs and pyrexia. Magnetic resonance imaging showed multifocal meningoencephalitis with transtentorial and foramen magnum herniation. A cerebrospinal fluid tap revealed highly cellular fluid, and the puppy was euthanized. Histopathology showed lymphoplasmacytic and neutrophilic meningoencephalitis. Viral polymerase chain reaction testing for Eastern equine encephalitis was positive. Rapid progression of neurologic signs and respiratory arrest necessitated mechanical ventilation. Severe hypernatremia, most consistent with central diabetes insipidus, developed.Key clinical message:Transtentorial and foramen magnum herniation and high cerebrospinal fluid cell counts may be indicators of poor prognosis. Brain death, respiratory arrest, and central diabetes insipidus may also ensue with Eastern equine encephalitis infection.     

Cerebrospinal fluid findings in cattle with central nervous system disorders: a retrospective study of 102 cases (1990–2008)

Background: Cerebrospinal fluid (CSF) analysis is routinely used to aid in the diagnosis of central nervous system (CNS) disease in animals. There is little comprehensive information available on the diagnostic utility of CSF analysis in cattle. Objectives: The purpose of this retrospective study was to review the characteristic CSF findings of specific CNS diseases in cattle. Methods: Medical records of cattle in which CSF analysis had been performed between 1990 and 2008 were reviewed. Cattle were included in the study if they had a confirmed diagnosis of CNS disease (based on clinical signs, laboratory testing, and/or histopathologic results). Cattle were categorized as having infectious or noninfectious causes of CNS disease and subgrouped based on specific disease diagnosis. CSF results were summarized and compared using nonparametric statistical tests. Results: Data from 102 cattle, mostly female Holsteins, were included in the study. Bacterial infections, particularly listeriosis and neonatal meningitis, were the most common cause of CNS disease. Neonatal meningitis was characterized by a marked, predominantly neutrophilic, pleocytosis. Mild mononuclear pleocytosis was typical of listeriosis, but was also seen with abscesses, viral infections, salt poisoning, and trauma. Variable CSF results were seen in cattle with otitis‐related meningitis and thromboembolic meningoencephalitis. CSF results were usually normal with toxic, metabolic, degenerative, and neoplastic disorders. Conclusions: CSF analysis is a useful adjunctive test for the diagnosis of CNS diseases in cattle. When interpreted together with signalment and clinical signs, CSF results can assist clinicians in the antemortem diagnosis of specific bovine CNS disorders.     

Meningioangiomatosis in young dogs: a case series and literature review

Meningioangiomatosis (MA) is a proliferative disorder of the central nervous system (CNS) that has been reported rarely in humans and sporadically in dogs. Meningioangiomatosis may occur in the brainstem or cervical spinal cord of young dogs and can be identified tentatively by magnetic resonance imaging. The histopathologic hallmark of MA is a leptomeningeal plaque that extends along the CNS microvasculature and invades the adjacent neural parenchyma. This case series describes the neurologic signs, clinical progression, diagnostic imaging, and neuropathology of 4 dogs with MA. The 4 dogs with MA are compared and contrasted with 4 previously reported cases in dogs as well as with their human counterpart.     

MAGNETIC RESONANCE IMAGING OF INTRACRANIAL INFLAMMATORY CONDITIONS IN DOGS: SENSITIVITY OF SUBTRACTION IMAGES VERSUS PRE‐ AND POST‐GADOLINIUM T1‐WEIGHTED IMAGE PAIRS

Ante mortem diagnosis of canine meningoencephalitis is usually based on the results of neurologic examination, cerebrospinal fluid analysis and magnetic resonance (MR) imaging. It has been hypothesized that subtraction MR imaging may increase the sensitivity of MR for intracranial inflammatory lesions compared to conventional post‐gadolinium T1‐weighted imaging. Sensitivity of pre‐ and post‐gadolinium (C‐/C+) image pairs and dynamic subtraction (DS) images was compared in a retrospective diagnostic accuracy study of 52 dogs with inflammatory cerebrospinal fluid and 67 dogs with idiopathic epilepsy. Series of transverse C‐/C+ and DS images were reviewed independently for signs of abnormal enhancement affecting the pachymeninges, leptomeninges or intra‐axial structures. Sensitivity of C‐/C+ image pairs and DS images was 48% (95% CI: 35–61%) and 65% (95% CI: 52–77%), respectively (P = 0.01). Intra‐axial lesions were observed more frequently than meningeal lesions in both C‐/C+ (43% vs. 31%) and DS images (61% vs. 22%). The difference in sensitivities of C‐/C+ and DS series was entirely due to increased sensitivity of DS images for intra‐axial lesions. Eight (12%) dogs with epilepsy had evidence of intra‐axial gadolinium accumulation affecting the cerebral cortex in DS images. This finding may represent a false‐positive result or a true sign of pathology, possibly associated with a leaky blood–brain barrier in areas of the brain affected by neovascularization secondary to repeated seizures. Results suggest that DS imaging has higher sensitivity than comparison of pre‐ and post‐gadolinium image pairs for inflammatory intra‐axial lesions.     

Imaging suppurative infections of the central nervous system in horses

Suppurative infections are typically caused by pyogenic bacteria, and are characterised by the formation of purulent exudates (pus). These infections may occur anywhere in the body and are particularly life‐threatening when pertaining to the central nervous system (CNS). Suppurative infections of the CNS may be due to trauma, local extension of disease, and haematogenous spread. In horses, suppurative infections are an important cause of morbidity and mortality, but only infrequently involve the CNS. The gross morphology of suppurative inflammation is described as phlegmon, abscess and empyema, with each form having characteristic morphological features that may be identified during advanced imaging of the CNS. In horses with known or suspected suppurative infection of the CNS, imaging may be performed to reduce diagnostic uncertainty, determine prognosis, or to describe the character and extent of the disease to guide case management.     

Acute postretinal blindness: ophthalmologic,neurologic, and magnetic resonance imaging findings in dogs and cats (seven cases)

Objective To describe the ophthalmologic, neurologic, and magnetic resonance imaging (MRI) findings of seven animals with acute postretinal blindness as sole neurologic deficit. Methods Medical records were reviewed to identify dogs and cats with postretinal blindness of acute presentation, that had a cranial MRI performed as part of the diagnostic workup. Only animals lacking other neurologic signs at presentation were included. Complete physical, ophthalmic, and neurologic examinations, routine laboratory evaluations, thoracic radiographs, abdominal ultrasound, electroretinography, and brain MRI were performed in all animals. Cerebrospinal fluid analysis and postmortem histopathologic results were recorded when available. Results Four dogs and three cats met the inclusion criteria. Lesions affecting the visual pathways were observed on magnetic resonance (MR) images in six cases. Location, extension, and MRI features were described. Neuroanatomic localization included: olfactory region with involvement of the optic chiasm (n = 4), pituitary fossa with involvement of the optic chiasm and optic tracts (n = 1), and optic nerves (n = 1). Of all lesions detected, five were consistent with intracranial tumors (two meningiomas, one pituitary tumor, two nasal tumors with intracranial extension), and one with bilateral optic neuritis that was confirmed by cerebrospinal fluid analysis. Histologic diagnosis was obtained in four cases and included one meningioma, one pituitary carcinoma, one nasal osteosarcoma, and one nasal carcinoma. Conclusions Central nervous system (CNS) disease should be considered in dogs and cats with acute blindness, even when other neurologic deficits are absent. This study emphasizes the relevance of MRI as a diagnostic tool for detection and characterization of CNS lesions affecting the visual pathways.     

Cerebrospinal Fluid PCR and Antibody Concentrations against Anaplasma phagocytophilum and Borrelia burgdorferi sensu lato in Dogs with Neurological Signs

Background: The tick-borne bacteria Borrelia burgdorferi sensu lato (sl) and Anaplasma phagocytophilum have been suspected to cause neurological signs in dogs. Diagnosis often has been made based on positive antibody titers in serum of dogs with neurological signs, but a high seroprevalence in dogs in at-risk populations makes diagnosis difficult.
Objective: To determine if the neurological signs in dogs examined were caused by any of these bacteria.
Animals: Fifty-four dogs presented to a board-certified neurologist.
Methods: Prospective study. We divided dogs into 2 groups: those with inflammatory diseases of the central nervous system (CNS) and those with neurological signs from other diseases. Blood and cerebrospinal fluid (CSF) from all dogs were analyzed.
Results: Dogs with inflammatory CNS diseases showed no serum antibodies against any of the agents. Among dogs with neurological signs from other diseases, 10.3% had serum antibodies for B. burgdorferi sl and 20.5% for A. phagocytophilum . All blood samples analyzed for bacterial deoxyribonucleic acid (DNA) and all CSF analyzed for antibodies and bacterial DNA for the 2 agents were negative.
Conclusions and Clinical Importance: Based on this study, these bacteria are unlikely causes of neurologic disease in dogs and the presence of serum antibodies alone does not document or establish a definitive diagnosis of CNS disease caused by these organisms. Dogs that have neurologic disease and corresponding serum antibodies against these agents should have additional tests performed to assess for other potential etiologies of the signs.     

Biofluid Markers of Equine Neurological Disorders Reviewed From Human Perspectives

Neurological disorders (NDs) are often fatal to horses. Thus, symptoms of equine NDs commonly indicate euthanasia. Current diagnostic approaches for equine NDs is based on clinical signs, differential diagnoses, analysis of cerebrospinal fluid (CSF), assessment of histopathological lesions, and imaging. However, advances in biofluid biomarkers in the diagnosis of human neurological diseases can potentially be applied to equine NDs. In this review, we described the established human blood and CSF neurobiomarkers that could potentially be used to diagnose equine NDs.     

Cerebrospinal fluid flow in normal beagle dogs analyzed using magnetic resonance imaging

BackgroundDiseases related to cerebrospinal fluid flow, such as hydrocephalus, syringomyelia, and Chiari malformation, are often found in small dogs. Although studies in human medicine have revealed a correlation with cerebrospinal fluid flow in these diseases by magnetic resonance imaging, there is little information and no standard data for normal dogs.ObjectivesThe purpose of this study was to obtain cerebrospinal fluid flow velocity data from the cerebral aqueduct and subarachnoid space at the foramen magnum in healthy beagle dogs.MethodsSix healthy beagle dogs were used in this experimental study. The dogs underwent phase-contrast and time-spatial labeling inversion pulse magnetic resonance imaging. Flow rate variations in the cerebrospinal fluid were observed using sagittal time-spatial labeling inversion pulse images. The pattern and velocity of cerebrospinal fluid flow were assessed using phase-contrast magnetic resonance imaging within the subarachnoid space at the foramen magnum level and the cerebral aqueduct.ResultsIn the ventral aspect of the subarachnoid space and cerebral aqueduct, the cerebrospinal fluid was characterized by a bidirectional flow throughout the cardiac cycle. The mean ± SD peak velocities through the ventral and dorsal aspects of the subarachnoid space and the cerebral aqueduct were 1.39 ± 0.13, 0.32 ± 0.12, and 0.76 ± 0.43 cm/s, respectively.ConclusionsNoninvasive visualization of cerebrospinal fluid flow movement with magnetic resonance imaging was feasible, and a reference dataset of cerebrospinal fluid flow peak velocities was obtained through the cervical subarachnoid space and cerebral aqueduct in healthy dogs.     

Neurologic dysfunction in hypothyroid, hyperlipidemic Labrador Retrievers

BACKGROUND: Hypothyroidism has been associated with a variety of neurologic signs, but the mechanism for this association is not completely understood. Hypothyroidism also is associated with hyperlipidemia that predisposes to atherosclerosis, increased blood viscosity, and thromboembolic events. OBJECTIVE: The objective is to characterize neurologic signs potentially associated with hyperlipidemia and atherosclerosis in canine hypothyroidism. ANIMALS: This study used dogs referred to North Carolina State University Veterinary Teaching Hospital for evaluation of neurologic signs. MATERIALS AND METHODS: A retrospective study was conducted in which medical records of dogs with neurologic signs and a diagnosis of hypothyroidism and hyperlipidemia were reviewed. Details of the history, presenting signs, results of routine blood tests, thyroid tests, cerebrospinal fluid (CSF) analysis and diagnostic imaging, and response to therapy were compiled. RESULTS: Three Labrador Retrievers and one Labrador Retriever cross fit the inclusion criteria. All dogs were hypothyroid and severely hyperlipidemic. Neurologic signs included tetraparesis, central and peripheral vestibular signs, facial paralysis, and paraparesis. Two dogs had an acute history and rapid resolution of signs consistent with an infarct, the presence of which was confirmed in 1 of the dogs by magnetic resonance imaging. Two dogs had chronic histories of cranial neuropathies and paraparesis. One of these dogs had evidence of iliac thrombosis and atherosclerosis on ultrasound examination. All dogs improved with thyroid hormone supplementation. CLINICAL RELEVANCE: Labrador Retrievers may be predisposed to the development of severe hyperlipidemia in association with hypothyroidism. One possible consequence of severe hyperlipidemia is the development of neurologic signs due to atherosclerosis and thromboembolic events.     

Angiostrongylus vasorum causing meningitis and detection of parasite larvae in the cerebrospinal fluid of a pug dog

This case report describes the presence of Angiostrongylus vasorum larvae in cerebrospinal fluid in an 11-month-old pug dog and the relative magnetic resonance images compatible with a focal meningitis. Clinical signs were compatible with a cerebellar lesion, and diagnosis was confirmed by parasitological analysis on faecal and endotracheal lavage samples. Treatment with fenbendazole and prednisolone resulted in a complete resolution of the clinical signs in two months time. A vasorum infection should be considered a possible aetiology of intracranial inflammation in dogs.     

Fibrocartilaginous embolic myelopathy in five cats

Five cats had clinical signs, radiographic findings, and cerebrospinal fluid analyses consistent with fibrocartilaginous embolic myelopathy. All cats had an acute onset of nonpainful, asymmetrical spinal cord signs (paresis or paralysis of one or more limbs). Magnetic resonance imaging was performed in three cats. On T2-weighted images, an intramedullary lesion was revealed that was hyperintense to normal spinal cord gray matter. On T1-weighted images, the lesion was isointense. Three of the cats were euthanized, and postmortem examination confirmed myelomalacia with intralesional fibrocartilaginous emboli. Two cats survived and were clinically improved within 3 weeks.