Clinical presentation, diagnostic findings, prognostic factors, treatment and outcome in dogs with meningoencephalomyelitis of unknown origin: A review.

Meningoencephalomyelitis of unknown origin (MUO) encompasses a group of idiopathic, most likely immune mediated, inflammatory central nervous system diseases that cause clinical, diagnostic and treatment challenges to veterinary neurologists. Clinical criteria for obtaining this presumptive diagnosis are currently available, and multiple treatment protocols have previously been investigated in small (prospective or retrospective) case series. As this group of diseases is considered fatal if left untreated, the identification of clinically usable prognostic indices could be of great value. This review provides an overview of recent developments in the clinical presentation, diagnostic findings, possible prognostic factors, treatment and outcome in dogs diagnosed with MUO.

Clinical presentation and magnetic resonance imaging findings in 11 dogs with eosinophilic meningoencephalitis of unknown aetiology.

OBJECTIVES: To describe the clinical presentation, MRI findings and outcome in dogs with eosinophilic meningoencephalitis of unknown origin. MATERIALS AND METHODS: Dogs were included in this retrospective study if they had complete medical records, complete neurological examination, MR imaging, cerebellomedullary cerebrospinal fluid sample consistent with eosinophilic pleocytosis and negative infectious disease testing. RESULTS: Eleven dogs were included with a median age of 22·0 months (range 7·6 to 92·0 months). Nine breeds were represented. Neurological abnormalities included obtundation (n=10), menace response deficits (n=9), proprioceptive deficits (n=7), ataxia (n=7) and seizures (n=2). Neuroanatomical localisation was multi-focal (n=4), central vestibular system (n=4), diffuse forebrain (n=2) or left trigeminal/facial nerves (n=1). Seven dogs had peripheral eosinophilia. Ten dogs had bilateral symmetrical lesions affecting the cortical grey matter, which was hyperintense on T2-weighted and fluid-attenuating inversion recovery images and iso- to hypointense on T1-weighted images with associated meningeal contrast enhancement. MRI findings were consistent with diffuse meningitis and atrophy or necrosis of cortical grey matter. One dog had increased contrast uptake in the left trigeminal nerve. Ten dogs receiving corticosteroids survived to discharge, with seven also receiving cytarabine arabinoside. Median survival time was 762 days. CLINICAL SIGNIFICANCE: Eosinophilic meningoencephalitis of unknown origin affects younger larger-breed dogs, with the majority having suspected diffuse cerebrocortical meningitis and cortical (polio)encephalitis, which can be identified on MRI. Response to immunosuppressive treatment is good in the medium to long term, although further studies are required in this area.

A dose-escalation study of combretastatin A4-phosphate in healthy dogs.

Combretastatin A4-Phosphate (CA4P) is a vascular disrupting agent revealing promising results in cancer treatments for humans. The aim of this study was to investigate the safety and adverse events of CA4P in healthy dogs as a prerequisite to application of CA4P in dogs with cancer. Ten healthy dogs were included. The effects of escalating doses of CA4P on physical, haematological and biochemical parameters, systolic arterial blood pressure, electrocardiogram, echocardiographic variables and general wellbeing were characterised. Three different doses were tested: 50, 75 and 100 mg m-2 . At all 3 CA4P doses, nausea, abdominal discomfort as well as diarrhoea were observed for several hours following administration. Likewise, a low-grade neutropenia was observed in all dogs. Doses of 75 and 100 mg m-2 additionally induced vomiting and elevation of serum cardiac troponine I levels. At 100 mg m-2 , low-grade hypertension and high-grade neurotoxicity were also observed. In healthy dogs, doses up to 75 mg m-2 seem to be well tolerated. The severity of the neurotoxicity observed at 100 mg m-2 , although transient, does not invite to use this dose in canine oncology patients.

A single dose of intravenous combretastatin A4-phosphate is reasonably well tolerated and significantly reduces tumour vascularization in canine spontaneous cancers.

Combretastatin A4-phosphate (CA4P) is an anti-tumour vascular targeting agent which selectively blocks tumour blood flow. Research on CA4P in rodent tumour models is extensive; however, knowledge of its effect on spontaneous cancer is scarce. This study was conducted in canine patients with spontaneous solid tumours. The goal was to assess the toxicity and efficacy of CA4P in various spontaneous tumour types. Eight dogs with spontaneous tumours were enrolled and treated with a single dose of 75 mg m-2 intravenous CA4P. The dogs were screened and monitored before and after injection. Pre- and post-treatment tumour blood flow was analysed in vivo by power Doppler ultrasound (PDUS) and contrast-enhanced ultrasound (CEUS). Vessel destruction and tumour necrosis were evaluated by histopathology. Clinically relevant toxicity was limited to one case of temporary tetraparesis; other adverse events were mild. Significant cardiovascular changes were mostly confined to changes in heart rate and cTnI levels. Macroscopic tumour size reduction was evident in 2 dogs. Based on PDUS and CEUS, CA4P induced a significant decrease in vascular index and tumour blood flow. Post-treatment, histopathology revealed a significant increase of necrotic tumoural tissue and a significant reduction in microvessel density in tumoural tissue. Anti-vascular and necrotizing effects of CA4P were documented in a variety of canine spontaneous cancers with only minimal side effects. This is the first study reporting the administration of CA4P to canine cancer patients with in vivo and ex vivo assessment, and a first step toward implementing CA4P in combination therapies in veterinary oncology patients. The use of CA4P in canine patients was approved and registered by the Belgian Federal Agency for Medicines and Health Products (FAMHP) (approval number 0002588, registration number 6518 ID 2F12).

Clinical presentation, diagnostic findings and outcome in dogs diagnosed withpresumptive spinal-only meningoen-cephalomyelitis of unknown origin.

OBJECTIVES: To summarise clinical presentation, diagnostic findings and long-term outcome for dogs clinically diagnosed with meningoencephalomyelitis of unknown origin affecting the spinal cord alone. METHODS: Medical records were reviewed for dogs diagnosed with presumptive spinal-only meningoencephalomyelitis of unknown origin between 2006 and 2015. RESULTS: 21 dogs were included; the majority presented with an acute (43%) or chronic (52%) onset of neurological signs. Ambulatory paresis was the most common neurological presentation (67%). Neurological examination most commonly revealed a T3-L3 myelopathy, and spinal hyperaesthesia was a common finding (71%). A spinal cord lesion was visible in 90% of cases on magnetic resonance imaging. Eighteen lesions (86%) showed parenchymal contrast enhancement and 17 lesions (81%) showed contrast enhancement of overlying meninges. All dogs were treated with immunosuppressive doses of glucocorticosteroids, sometimes combined with cytosine arabinoside. At time of data capture, 10/21 dogs (48%) had died or been euthanased because of the condition. Overall median survival time was 669 days. CLINICAL SIGNIFICANCE: Meningoencephalomyelitis of unknown origin should be considered in the differential diagnosis of dogs presenting with a progressive myelopathy. Magnetic resonance imaging features can possibly help to distinguish presumptive meningoencephalomyelitis of unknown origin from other more common spinal diseases. Overall, long-term survival is guarded, approximately 50% of dogs will die or be euthanased despite appropriate therapy.

Clinical presentation, diagnostic findings and long-term survival in large breed dogs with meningoencephalitis of unknown aetiology.

Although several studies indicate that meningoencephalitis of unknown aetiology (MUA) might affect every dog breed at every age, little is known about clinical presentation, diagnostic findings and long-term survival in large breed dogs. The aim of this study was therefore to compare the clinical presentation, diagnostic findings and long-term survival between large and small/medium breed dogs diagnosed with MUA. One hundred and eleven dogs met the inclusion criteria. 28 (25 per cent) dogs were considered large breed dogs compared with 83 (75 per cent) small/medium breed dogs. Large breed dogs presented significantly more often with a decreased mentation. Age, gender, duration of clinical signs prior to diagnosis, presence of seizures or cluster seizures, variables on complete blood count and cerebrospinal fluid analysis, and all variables on MRI were not significantly different between small/medium and large breed dogs. Median survival time was 281 and 106 days for the large and small/medium breed dogs, respectively, with no significant difference in survival curves for both groups. Although considered not typically affected by MUA, 25 per cent of dogs included in this study were considered large breed dogs. Therefore, MUA should be included in the differential diagnosis for large breed dogs presenting with intracranial neurological signs. If diagnosed with MUA, large breed dogs also carried a guarded prognosis.

Postoperative symptomatic haematoma and pneumorrhachis in a dog with a thoracolumbar intervertebral disc extrusion.

CASE REPORT: A 6-year-old male neutered crossbreed dog presented with acute onset paraparesis and was diagnosed with an L1-L2 intervertebral disc extrusion. A right-sided T13-L2 hemilaminectomy was performed. However, the dog deteriorated and became paraplegic with marked thoracolumbar hyperaesthesia 48 h after surgery. A computed tomography scan of the thoracolumbar vertebral column revealed the presence of pneumorrhachis (PR) at the level of T13, possibly embedded in a haematoma, and causing marked spinal cord compression. Revision surgery confirmed the presence of a haematoma, which was removed. The dog gradually improved and was neurologically normal 6 weeks after surgery. CONCLUSION: Although PR is a rare condition, it may be considered a possible cause for early postoperative neurological deterioration in dogs undergoing decompressive spinal surgery. Surgical revision resulted in a good outcome in the presented case.

Prognostic factors for 1-week survival in dogs diagnosed with meningoencephalitis of unknown aetiology.

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.

Unilateral shunt formation with thoracic aortic dissection in a whippet.

A three-year-old neutered male whippet was presented with intermittent, exercise-induced paraparesis. Femoral pulses were bilaterally absent. Neurologic examination was suggestive of a thoracolumbar myelopathy. Blood pressure measurements revealed hypotension in both pelvic limbs, hypertension in the right thoracic limb and it was immeasurable in the left thoracic limb. Echocardiography was within reference limits. A clear vascular pulsation was palpable on the right ventral abdominal wall. Computed tomographic angiography revealed a dissection of the aortic wall between the left subclavian artery and the brachiocephalic trunk with subsequent thrombus formation. A shunt between the right internal thoracic, cranial and caudal epigastric arteries to preserve blood flow to the pelvic limbs was visualized. Necropsy was declined by the owner. This is the first case report describing the formation of a unilateral vascular shunt following a thoracic aortic occlusion, which presented as exercise-induced paraparesis.

Claudin-1 and glucose transporter 1 immunolabelling in a canine intraneural perineurioma.

A 4-year-old male leonberger was diagnosed tentatively with a peripheral nerve sheath tumour of the median nerve based on neurological examination, electrodiagnostic testing and ultrasound evaluation. The lesion was excised and submitted for pathological examination. Histopathology revealed an irregularly enlarged, hypercellular nerve fascicle with neoplastic tissue consisting of a uniform population of spindle-shaped cells arranged in 'pseudo-onion bulb-like' whorls around axons. Minimal anisocytosis and anisokaryosis were present, together with a low mitotic index. Electron microscopy showed spindle cells with a discontinuous basal membrane and intercellular junctions, as well as pinocytotic vesicles. Immunohistochemistry for neurofilament, S100 and glucose transporter 1 was negative, whereas labelling for claudin-1 and laminin was positive. Based on these observations, a definitive diagnosis of intraneural perineurioma was made.

Ultrasound-guided sentinel node procedure for nonpalpable breast carcinoma.

PURPOSE: Peritumoral and periareolar tracer injection techniques lead to different lymphatic drainage in sentinel lymph node biopsy procedures. In a prospective study, the visualization and identification rates of the ultrasound (US)-guided tracer injection technique for palpable and nonpalpable breast tumors were evaluated. METHODS: In 1262 consecutive patients with cT1₋2N0 breast cancer, sentinel lymph node biopsy was performed following peritumoral tracer injection. In the case of nonpalpable breast lesions, Tc-99m nanocolloid injections were given using a 7.5 MHz US probe. In the case of ultrasonographically nonvisible microcalcifications, the US-guided injection technique was wire guided. RESULTS: In 331 patients with nonpalpable breast lesions (26.2%), the lymphoscintigraphic visualization and surgical retrieval rates of axillary sentinel lymph nodes (SLNs) were 98.5 and 99.4%, respectively. For internal mammary (IM) SLNs, these rates were 21.1 and 17.8%, respectively. These rates were similar in patients with palpable and nonpalpable tumors. Axillary metastases were detected in 38.7% of the patients with palpable tumors versus 16.5% of those with nonpalpable tumors (P<0.001), whereas IM metastases were found in 4.8 and 3.0% of patients, respectively (P=0.165). CONCLUSION: In nonpalpable breast lesions, the US-guided injection technique is an accurate technique for SLN identification and retrieval. The substantial rates of IM metastases in both palpable and nonpalpable lesions favor a peritumoral tracer injection technique.