Immune-mediated polyneuropathy in cats: Clinical description, electrodiagnostic assessment, and treatment.

BACKGROUND: Suspected immune-mediated polyneuropathy has been increasingly reported in cats, especially in the last decade, but the condition remains poorly understood. OBJECTIVES: Refine the clinical description and review the classification of this condition based on electrodiagnostic investigation and evaluate the benefit of corticosteroid treatment and L-carnitine supplementation. ANIMALS: Fifty-five cats presented with signs of muscular weakness and electrodiagnostic findings consistent with polyneuropathy of unknown origin. METHODS: Retrospective, multicenter study. Data from the medical records were reviewed. The owners were contacted by phone for follow-up at the time of the study. RESULTS: The male-to-female ratio was 2.2. The median age of onset was 10 months, with 91% of affected cats being <3 years of age. Fourteen breeds were represented in the study. The electrodiagnostic findings supported purely motor axonal polyneuropathy. Histological findings from nerve biopsies were consistent with immune-mediated neuropathy in 87% of the tested cats. The overall prognosis for recovery was good to excellent, as all but 1 cat achieved clinical recovery, with 12% having mild sequelae and 28% having multiple episodes during their lifetime. The outcome was similar in cats with no treatment when compared with cats receiving corticosteroids or L-carnitine supplementation. CONCLUSIONS AND CLINICAL IMPORTANCE: Immune-mediated motor axonal polyneuropathy should be considered in young cats with muscle weakness. This condition may be similar to acute motor axonal neuropathy in Guillain-Barré syndrome patients. Based on our results, diagnostic criteria have been proposed.

Biopsy Characteristics, Subtypes, and Prognostic Features in 107 Cases of Feline Presumed Immune-Mediated Polyneuropathy.

Inflammatory polyradiculoneuropathy (IMPN) is one of the causes of sudden onset of neuromuscular signs such as para-/tetraparesis in young cats. Even though most cases have a favorable outcome, persistent deficits, relapses, and progressive courses are occasionally seen. As clinical presentation does not always appear to predict outcome and risk of recurrence, this study was initiated to screen for prognostic biopsy findings in a large cohort of histologically confirmed IMPN cases with clinical follow-up. In total, nerve and muscle specimens of 107 cats with biopsy diagnosis of presumed autoreactive inflammatory polyneuropathy and 22 control cases were reviewed by two blinded raters for a set of 36 histological parameters. To identify patterns and subtypes of IMPN, hierarchical k-means clustering of 33 histologic variables was performed. Then, the impact of histological parameters on IMPN outcome was evaluated via an univariate analysis to identify variables for the final multivariate model. The data on immediate outcome and follow-up were collected from submitting neurologists using a purpose-designed questionnaire. Hierarchical k-means clustering sorted the tissues into 4 main categories: cluster 1 (44/129) represents a purely inflammatory IMPN picture, whereas cluster 2 (47/129) was accompanied by demyelinating features and cluster 3 (16/129) by Wallerian degeneration. Cluster 4 (22/129) reflects normal tissues from non-neuropathic control cats. Returned questionnaires provided detailed information on outcome in 63 animals. They were categorized into recovered and non-recovered. Thereby, fiber-invasive infiltrates by mononuclear cells and mild fiber loss in intramuscular nerve branches correlated with higher probabilities of recovery. Remyelination in semithin sections, on the other hand, is correlated with a less favorable outcome. Animals grouping in cluster 1 had a tendency to a higher probability of recovery compared to other clusters. In conclusion, diagnosis of feline IMPN from nerve and muscle biopsies allowed for the identification of histologic features that were positively or negatively correlated with outcome.

Clinical Course and Diagnostic Findings of Biopsy Controlled Presumed Immune-Mediated Polyneuropathy in 70 European Cats.

There is a paucity of information on the clinical course and outcome of young cats with polyneuropathy. The aim of the study was to describe the clinical features, diagnostic investigations, and outcome of a large cohort of cats with inflammatory polyneuropathy from several European countries. Seventy cats with inflammatory infiltrates in intramuscular nerves and/or peripheral nerve biopsies were retrospectively included. Information from medical records and follow up were acquired via questionnaires filled by veterinary neurologists who had submitted muscle and nerve biopsies (2011-2019). Median age at onset was 10 months (range: 4-120 months). The most common breed was British short hair (25.7%), followed by Domestic short hair (24.3%), Bengal cat (11.4%), Maine Coon (8.6%) and Persian cat (5.7%), and 14 other breeds. Male cats were predominantly affected (64.3%). Clinical signs were weakness (98.6%) and tetraparesis (75.7%) in association with decreased withdrawal reflexes (83.6%) and, less commonly, cranial nerve signs (17.1%), spinal pain/hyperesthesia (12.9%), and micturition/defecation problems (14.3%). Onset was sudden (30.1%) or insidious (69.1%), and an initial progressive phase was reported in 74.3%. Characteristic findings on electrodiagnostic examination were presence of generalized spontaneous electric muscle activity (89.6%), decreased motor nerve conduction velocity (52.3%), abnormal F-wave studies (72.4%), pattern of temporal dispersion (26.1%) and unremarkable sensory tests. The clinical course was mainly described as remittent (49.2%) or remittent-relapsing (34.9%), while stagnation, progressive course or waxing and waning were less frequently reported. Relapses were common and occurred in 35.7% of the cats' population. An overall favorable outcome was reported in 79.4% of patients. In conclusion, young age at the time of diagnosis and sudden onset of clinical signs were significantly associated with recovery (p < 0.05). Clinical and electrodiagnostic features and the remittent-relapsing clinical course resembles juvenile chronic inflammatory demyelinating polyneuropathy (CIDP), as seen in human (children/adolescents), in many aspects.

Brain perfusion magnetic resonance imaging using pseudocontinuous arterial spin labeling in 314 dogs and cats.

BACKGROUND: Arterial spin labeling (ASL) is a noninvasive brain perfusion magnetic resonance imaging (MRI) technique that has not been assessed in clinical veterinary medicine. HYPOTHESIS/OBJECTIVES: To test the feasibility of ASL using a 1.5 Tesla scanner and provide recommendations for optimal quantification of cerebral blood flow (CBF) in dogs and cats. ANIMALS: Three hundred fourteen prospectively selected client-owned dogs and cats. METHODS: Each animal underwent brain MRI including morphological sequences and ≥1 ASL sequences using different sites of blood labeling and postlabeling delays (PLD). Calculated ASL success rates were compared. The CBF was quantified in animals that had morphologically normal brain MRI results and parameters of ASL optimization were investigated. RESULTS: Arterial spin labeling was easily implemented with an overall success rate of 95% in animals with normal brain MRI. Technical recommendations included (a) positioning of the imaging slab at the foramen magnum and (b) selected PLD of 1025 ms in cats and dogs <7 kg, 1525 ms in dogs 7 to 38 kg, and 2025 ms in dogs >38 kg. In 37 dogs, median optimal CBF in the cortex and thalamic nuclei were 114 and 95 mL/100 g/min, respectively. In 28 cats, median CBF in the cortex and thalamic nuclei were 113 and 114 mL/100 g/min, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Our survey of brain perfusion ASL-MRI demonstrated the feasibility of ASL at 1.5 Tesla, suggested technical recommendations and provided CBF values that should be helpful in the characterization of various brain diseases in dogs and cats.

Clinical and serologic remission of acquired myasthenia gravis in a domestic ferret (Mustela putorius furo).

CASE DESCRIPTION: A 4.5-year-old neutered male domestic ferret (Mustela putorius furo) was examined because of clinical signs compatible with neuromuscular disease. CLINICAL FINDINGS: Results of electrophysiologic assessment, including measurement of compound muscle action potentials following repetitive nerve stimulation, and measurement of the anti-acetylcholine receptor antibody titer were consistent with a diagnosis of acquired myasthenia gravis. TREATMENT AND OUTCOME: Medical treatment with pyridostigmine and prednisolone was instituted. The first signs of clinical improvement were observed 2 months later, followed by a slow but steady improvement over the next months. Anti-acetylcholine receptor antibody titer was measured 10 months after initiation of treatment and was markedly decreased, compared with the initial titer. Pyridostigmine and prednisolone dosages were tapered over the following 4 months without any evidence of recurrence of clinical signs. Thirty months after initial examination, the ferret was clinically normal and not receiving any treatment. A follow-up anti-acetylcholine receptor antibody titer was similar to previously published values for healthy ferrets. CLINICAL RELEVANCE: Findings indicated that clinical and serologic remission can be achieved in ferrets with myasthenia gravis. However, owner willingness to provide extensive supportive care was vital to the outcome for this patient, as was the owner's decision to not euthanize the ferret despite an initial lack of response to treatment.

Evaluation of coexisting polymyositis in feline myasthenia gravis: A case series.

Acquired myasthenia gravis (MG) is relatively uncommon in cats. In humans, MG may be associated with other immune-mediated disorders, in particular polymyositis (PM). In this study, we described in-depth electrodiagnostic findings and pathological changes in muscles of cats diagnosed with MG, and assessed the presence of concurrent PM. Six cats with confirmed acetylcholine receptor antibody seropositive MG, and two suspected cases with clinical signs and electrophysiological changes consistent with MG, were reviewed. All animals presented with severe typical signs of generalized weakness and/or fatigability, resembling late-onset MG in humans, in addition to regurgitation. Five cats presented a cranial mediastinal mass, with 3 confirmed as thymoma. Repetitive nerve stimulation revealed a decrement of the compound muscle action potential in all tested cases, starting from low frequencies of stimulation. Serum creatine kinase activity was increased in 6/8 cats. Muscle biopsies performed in 5 cats revealed varying degrees of mixed mononuclear cell infiltrates, positive for the leukocyte markers CD3/CD4/CD8 and CD11b. Further MHC-1/C5b-9 positive sarcolemmal deposits were identified in all tested cases, with or without thymoma. This study documents an association of MG and PM in cats, and provides further support for feline MG as a relevant animal model of human MG.

Nodo-paranodopathy, internodopathy and cleftopathy: Target-based reclassification of Guillain-Barré-like immune-mediated polyradiculoneuropathies in dogs and cats.

Recent views on Guillain-Barré syndrome (GBS) question the accuracy of classification into axonal and demyelinating subtypes that represent convergent neurophysiological phenotypes rather than immunological targets. Instead it has been proposed to clarify the primarily affected fibre subunit in nerve biopsies. As nerve biopsies rarely are part of routine work-up in human patients we evaluated tissues taken from companion animals affected by GBS-like polyradiculoneuropathy to screen for distribution of immune cells, targeted fibre components and segregating non-inflammatory lesions. We identified that immune responses were directed either at Schmidt-Lanterman clefts, the paranode-node complex or both. Based on infiltrative and non-inflammatory changes, four subtypes and/or stages were distinguished, some of which indicate localisation of primary target antigens while others represent convergent late stage pictures, as a consequence to epitope spreading. The impact of histological subtyping onto clinical management and prognosis remains to be evaluated in future clinical trials. Natural development and clinical manifestation of large animal dysimmune neuropathy may reflect human Guillain-Barré syndrome more accurately than experimental models and therefore provide complementary clues for translational research.

Presence of neural progenitors in spontaneous canine gliomas: A histopathological and immunohistochemical study of 20 cases.

Gliomas are the most common primary brain tumours in humans and are associated with a poor prognosis. An accurate animal model of human glioma tumorigenesis is needed to test new treatment strategies. Dogs represent a promising model because they develop spontaneous diffusely-infiltrating gliomas. This study investigated whether spontaneous canine gliomas contain cancer stem cells previously identified in all grades of human gliomas. Twenty spontaneous cases of canine gliomas were graded according to the human WHO classification. The expression of different markers of lineage differentiation was evaluated with immunohistochemistry as follows: nestin and CD133 for neural stem cells, doublecortin for neuronal progenitor cells, Olig2 for glial progenitor cells, glial fibrillary acidic protein, vimentin and S-100 for mature glial cells, and NeuN and ßIII-tubulin for mature neurons. Gliomas were characterised as follows: five grade II (oligodendrogliomas); nine grade III (seven anaplastic oligodendrogliomas, one anaplastic astrocytoma, one anaplastic oligoastrocytoma); six grade IV (glioblastomas). Immunohistochemical evaluation revealed that (1) nestin and CD133 were expressed in all grades of gliomas with a higher proportion of positive cells in high-grade gliomas; (2) the expression of S-100 protein and Olig2 did not differ substantially between astrocytic and oligodendroglial tumours, and (3) all gliomas were negative for mature neuron markers. The results demonstrated the presence of undifferentiated neural progenitors in all grades of spontaneous canine gliomas, confirming the relevance of this animal model for further studies on cancer stem cells.

Prevalence of deafness and association with coat variations in client-owned ferrets.

OBJECTIVE: To evaluate the prevalence of congenital sensorineural deafness (CSD) and its association with phenotypic markers in client-owned ferrets. DESIGN: Epidemiological study. ANIMALS: 152 healthy European pet ferrets. PROCEDURES: Brainstem auditory evoked response tests were recorded in ferrets during general anesthesia. Phenotypic markers such as sex, coat color and pattern, coat length (Angora or not), and premature graying trait were assessed. RESULTS: Overall, 44 of the 152 (29%) ferrets were affected by CSD; 10 (7%) were unilaterally deaf, and 34 (22%) were bilaterally deaf. There was no association between CSD and sex or Angora trait, but a strong association between CSD and white patterned coat or premature graying was identified. All panda, American panda, and blaze ferrets were deaf. CONCLUSIONS AND CLINICAL RELEVANCE: The ferrets in this study had a high prevalence of CSD that was strictly associated with coat color patterns, specifically white markings and premature graying. This seemed to be an emerging congenital defect in pet ferrets because white-marked coats are a popular new coat color. Breeders should have a greater awareness and understanding of this defect to reduce its prevalence for the overall benefit of the species.

Successful treatment of cervical spinal epidural empyema secondary to grass awn migration in a cat.

Spinal epidural empyema (SEE) represents a severe pyogenic infection of the epidural space. Clinical signs of the disease are non-specific--increased body temperature, intense neck pain, neurological signs of a transverse myelopathy--and can lead to severe and permanent neurological deficits. This report describes the diagnosis and successful surgical treatment of cervical SEE secondary to grass awn migration in a cat. Although it is uncommon, this disease should be suspected in cats with progressive myelopathy. Early diagnosis and emergency surgery combined with antibiotic therapy are required to allow a complete recovery.

Cutaneous saphenous nerve graft for the treatment of sciatic neurotmesis in a dog.

CASE DESCRIPTION: A 2-year-old Griffon Vendéen was examined because of a 1-month history of right hind limb lameness after a traumatic injury. CLINICAL FINDINGS: Neurologic examination revealed monoplegia and anesthesia of the right hind limb distal to the stifle (femorotibial) joint except for the area supplied by the cutaneous saphenous nerve. Results of electromyographic testing were consistent with a severe lesion of the tibial and peroneal nerves at the level of the stifle joint. TREATMENT AND OUTCOME: Exploratory surgery revealed an 80-mm-long gap in both the peroneal and tibial branches of the right sciatic nerve. A section of the left cutaneous saphenous nerve was interposed to graft the nerve defects. The dog received joint mechanotherapy and electrophysiologic therapy during the reinnervation process. Ten months after surgery, the dog had recovered almost completely. Neurologic examination revealed diminished flexion of the tarsal and digital joints. Repeat electromyographic testing revealed no abnormal spontaneous electrical activity in the right hind limb musculature, and small compound muscle action potentials were recorded in the right interosseous and cranial tibial muscles. CLINICAL RELEVANCE: Without surgical treatment, neurotmesis injury results in poor recovery of motor and sensory functions and may result in amputation. If a nerve defect exists, nerve grafting should be considered, even if the procedure is delayed until well after the injury. The sensory portion of the cutaneous saphenous nerve is a potential source of peripheral nerve for grafting in dogs. Reinnervation is a long-term process and physiologic support and owner involvement are necessary, but nearly complete functional recovery is possible.

Restoration of elbow flexion by performing contralateral lateral thoracic and thoracodorsal nerve transfers after experimental musculocutaneous nerve transection.

OBJECT: The immediate transfer of the right lateral thoracic nerve (LTN) and the thoracodorsal nerve (TDN) to the transected left musculocutaneous nerve (MCN), leading to nerve cross-neurotization, was performed in cats to evaluate reinnervation of the biceps brachii muscle (BBM). METHODS: Surgery to produce cross-neurotization of the MCN was performed in 12 cats (treatment group). Transection of the MCN was performed without attempts at neurotization in three cats (control group). Reinnervation of the BBM was assessed by performing electromyography (EMG) 6 months (14 cats) and 26 months (one cat) postsurgery. True Blue retrograde axonal tracing studies, tensile force measurements (muscle extensometry), and histopathological analyses were performed. All cats in the treatment group recovered voluntary contraction of the BBM and regained elbow flexion. Electromyography revealed no abnormal spontaneous activity in the BBM. Muscle evoked potentials were recorded in that muscle after right C-8 ventral branch stimulation. The muscle contraction strength in the left BBM varied from 108 to 557 g. The BBMs regained their normal appearances. The region of the MCN distal to the anastomosis displayed a normal histological appearance. Fluorescence was detected in the ventral horn of the spinal cord in the right C-8 and T-1 segments. In contrast, in all cats in the control group there was atrophy of the BBM, no EMG signal, and no clinical sign of recovery. There was no contraction of the BBM, no labeled neuron in the spinal cord, and the MCN displayed major degenerative changes. CONCLUSIONS: These findings demonstrate that the LTN and TDN can be used to neurotize injured contralateral brachial plexus nerves and obtain successful reinnervation in cats.

Cutaneous manifestations of neurological diseases: review of neuro-pathophysiology and diseases causing pruritus.

Pruritus does not always originate from stimulation to the skin associated with primary dermatological disorders. It may be caused by neurological or behavioural disorders. The essential role of the nervous system in the control (enhancement and inhibition) of pruritus and its pathophysiology are presented. In order to allow differentiation between dermatological and neurological disorders, inherited or acquired peripheral neuropathies and central nervous disorders (Arnold-Chiari syndrome, seizure-related disorders, central nervous system tumours) that may induce itch are discussed.

Spinal subarachnoid cysts in 13 dogs.

Thirteen dogs, including 6 Rottweiler dogs, exhibiting clinical signs of spinal cord dysfunction and myelographically confirmed subarachnoid space enlargement were investigated. To characterize the lesions and to get a better understanding of their pathogenesis, different imaging techniques were used in association with explorative surgical procedures (12 dogs) and histopathologic techniques (5 dogs). All subjects underwent preoperative myelography, five of which were examined by computed tomography (CT) scanning and one by magnetic resonance imaging (MRI) as well as cerebrospinal fluid (CSF) flow measurement (velocimetry). Most animals were <12 months old (7/13 dogs) and Rottweilers were over-represented (6/13 dogs). The lesions were mainly located dorsally with respect to the spinal cord (10/13 dogs) and in the cranial cervical area (8/13 dogs). MRI suggested spinal cord deviation with signs of ventral leptomeningeal adhesion opposite the enlarged space. In one dog, velocimetry confirmed that the "cyst" was freely communicating with the surrounding CSF space. Surgical investigation confirmed leptomeninges-induced ventral adhesion in 4/5 dogs. Follow-up studies, carried out from 6 months to 2.5 years postoperatively, showed there was full recovery in 8/13 dogs. This study suggests that the compression of the spinal cord is possibly not caused by a cyst. Adhesion resulting from a combination of microtrauma and chronic inflammatory processes induces a secondary enlargement of the subarachnoid space and may be a significant causative factor in spinal cord compression and dysfunction. The over-representation of Rottweilers and the young age of the animals in the study suggest a possible genetic predisposition and an inherited etiology.