Parallel roles of neuroinflammation in feline and human epilepsies.

Autoimmune encephalitis refers to a group of disorders characterised by a non-infectious encephalitis, often with prominent seizures and surface neuronal autoantibodies. AE is an important cause of new-onset refractory status epilepticus in humans and is frequently responsive to immunotherapies including corticosteroids, plasma exchange, intravenous immunoglobulin G and rituximab. Recent research suggests that parallel autoantibodies can be detected in non-human mammalian species. The best documented example is leucine-rich glioma-inactivated 1 (LGI1)-antibodies in domestic cats with limbic encephalitis (LE). In this review, we discuss the role of neuroinflammation and autoantibodies in human and feline epilepsy and LE.

Cerebrospinal fluid analysis lacks diagnostic specificity in dogs with vestibular disease.

BACKGROUND: Although, vestibular syndrome is a common neurological presentation, little is known about the diagnostic value of cerebrospinal fluid (CSF) analysis in vestibular syndrome in dogs. METHODS: Medical records were retrospectively reviewed, and dogs with vestibular disease that had undergone magnetic resonance imaging of the head, CSF analysis and were diagnosed with central or peripheral vestibular syndrome were included. Disorders affecting the central vestibular system included meningoencephalitis of unknown origin (MUO), brain neoplasia, ischaemic infarct, intracranial empyema or metronidazole toxicity. Disorders affecting the peripheral vestibular system included idiopathic vestibular disease, otitis media/interna or neoplasia affecting the inner ear structures. Total nucleated cell concentration (TNCC), total protein concentration (TP) and cytologic assessment were recorded. RESULTS: A total of 102 dogs met the inclusion criteria. The sensitivity and specificity of increased CSF TNCC to differentiate central from peripheral vestibular syndrome was 49% and 90%, while the sensitivity and specificity of increased TP was 58% and 39%, respectively. The TNCC and TP in dogs with MUO were significantly higher than in dogs with idiopathic vestibular disease (p = 0.000 and p = 0.004). MUO was associated with lymphocytic pleocytosis, while idiopathic vestibular disease and ischaemic infarct were associated with the presence of activated macrophages or normal cytology (p = 0.000). CONCLUSION: Although consistent CSF abnormalities were observed in dogs with MUO, CSF analysis did not allow reliable differentiation between central and peripheral vestibular syndrome. CSF analysis is not reliable as the sole diagnostic technique in dogs with vestibular disease.

Human-relevant near-organ neuromodulation of the immune system via the splenic nerve.

Neuromodulation of immune function by stimulating the autonomic connections to the spleen has been demonstrated in rodent models. Consequently, neuroimmune modulation has been proposed as a new therapeutic strategy for the treatment of inflammatory conditions. However, demonstration of the translation of these immunomodulatory mechanisms in anatomically and physiologically relevant models is still lacking. Additionally, translational models are required to identify stimulation parameters that can be transferred to clinical applications of bioelectronic medicines. Here, we performed neuroanatomical and functional comparison of the mouse, rat, pig, and human splenic nerve using in vivo and ex vivo preparations. The pig was identified as a more suitable model of the human splenic innervation. Using functional electrophysiology, we developed a clinically relevant marker of splenic nerve engagement through stimulation-dependent reversible reduction in local blood flow. Translation of immunomodulatory mechanisms were then assessed using pig splenocytes and two models of acute inflammation in anesthetized pigs. The pig splenic nerve was shown to locally release noradrenaline upon stimulation, which was able to modulate cytokine production by pig splenocytes. Splenic nerve stimulation was found to promote cardiovascular protection as well as cytokine modulation in a high- and a low-dose lipopolysaccharide model, respectively. Importantly, splenic nerve-induced cytokine modulation was reproduced by stimulating the efferent trunk of the cervical vagus nerve. This work demonstrates that immune responses can be modulated by stimulation of spleen-targeted autonomic nerves in translational species and identifies splenic nerve stimulation parameters and biomarkers that are directly applicable to humans due to anatomical and electrophysiological similarities.

Imaging of focal seizures with Electrical Impedance Tomography and depth electrodes in real time.

Intracranial EEG is the current gold standard technique for localizing seizures for surgery, but it can be insensitive to tangential dipole or distant sources. Electrical Impedance Tomography (EIT) offers a novel method to improve coverage and seizure onset localization. The feasibility of EIT has been previously assessed in a computer simulation, which revealed an improved accuracy of seizure detection with EIT compared to intracranial EEG. In this study, slow impedance changes, evoked by cell swelling occurring over seconds, were reconstructed in real time by frequency division multiplexing EIT using depth and subdural electrodes in a swine model of epilepsy. EIT allowed to generate repetitive images of ictal events at similar time course to fMRI but without its significant limitations. EIT was recorded with a system consisting of 32 parallel current sources and 64 voltage recorders. Seizures triggered with intracranial injection of benzylpenicillin (BPN) in five pigs caused a repetitive peak impedance increase of 3.4 ± 1.5 mV and 9.5 ± 3% (N =205 seizures); the impedance signal change was seen already after a single, first seizure. EIT enabled reconstruction of the seizure onset 9 ± 1.5 mm from the BPN cannula and 7.5 ± 1.1 mm from the closest SEEG contact (p<0.05, n =37 focal seizures in three pigs) and it could address problems with sampling error in intracranial EEG. The amplitude of the impedance change correlated with the spread of the seizure on the SEEG (p <<0.001, n =37). The results presented here suggest that combining a parallel EIT system with intracranial EEG monitoring has a potential to improve the diagnostic yield in epileptic patients and become a vital tool in improving our understanding of epilepsy.

Ventral Slot Surgery to Manage Cervical Intervertebral Disc Disease in Three Cats.

OBJECTIVE: This case series describes the clinical presentation, management and outcome of three cats diagnosed with cervical intervertebral disc disease that underwent decompressive ventral slot surgery. METHODS: This is a retrospective case series evaluating client-owned cats undergoing a ventral slot surgical procedure to manage cervical intervertebral disc disease (n = 3). RESULTS: A routine ventral slot surgery was performed in each case without complication, resulting in postoperative neurological improvement in all three cases. CLINICAL SIGNIFICANCE: Ventral slot surgery can be used to achieve effective cervical spinal cord decompression with a good long-term outcome in the management of feline cervical intervertebral disc herniation. To avoid creating an excessively wide slot with the potential for postoperative complications including vertebral sinus haemorrhage, vertebral instability or ventral slot collapse, careful surgical planning was performed with preoperative measurement of the desired maximum slot dimensions.

Surgical treatment of a paraspinal abscess with osteomyelitis and spinal cord compression in a rabbit.

CASE DESCRIPTION A 16-month-old neutered male Continental Giant rabbit (Lepus curpaeums) was referred for evaluation of a 7-day history of acute-onset, progressive, symmetric paraparesis. CLINICAL FINDINGS On initial examination, the rabbit was nonambulatory, and results of neurologic examination were consistent with a lesion affecting the T3-L3 spinal cord segments. Thoracic radiography showed irregular widening of the left T11-12 articular process joint. Marked dorsolateral and lateral extradural spinal cord compression with contrast enhancement of the adjacent epaxial muscles was evident on MRI images of the spine. TREATMENT AND OUTCOME A left-sided T11-T12 hemilaminectomy was performed, which revealed an abnormal and hypertrophic T11-12 articular process joint and an osteolytic lesion communicating with the vertebral canal. Copious purulent material causing marked spinal cord compression was evident, and the surgical site was lavaged extensively with sterile (0.9% NaCl) saline solution. Results of aerobic, anaerobic, and enriched bacteriologic cultures of swab specimens obtained from the surgical site were negative. Histologic analysis of biopsy samples revealed chronic purulent osteomyelitis, myositis, and fasciitis with necrosis, fibrosis, and dystrophic mineralization. The rabbit was discharged 48 hours after surgery. Ten weeks after surgery, the rabbit was ambulatory with mild paraparesis. On telephone follow-up 21 months after surgery, the owners indicated that the rabbit was healthy and expressed satisfaction with the treatment and outcome. CLINICAL RELEVANCE Paraspinal abscess with vertebral canal involvement should be considered as a differential diagnosis for rabbits with clinical signs of progressive T3-L3 myelopathy. Outcome for the patient of the present report suggested that surgical treatment including decompression and debridement can result in a favorable long-term outcome.

Retinoid X receptor activation reverses age-related deficiencies in myelin debris phagocytosis and remyelination.

The efficiency of central nervous system remyelination declines with age. This is in part due to an age-associated decline in the phagocytic removal of myelin debris, which contains inhibitors of oligodendrocyte progenitor cell differentiation. In this study, we show that expression of genes involved in the retinoid X receptor pathway are decreased with ageing in both myelin-phagocytosing human monocytes and mouse macrophages using a combination of in vivo and in vitro approaches. Disruption of retinoid X receptor function in young macrophages, using the antagonist HX531, mimics ageing by reducing myelin debris uptake. Macrophage-specific RXRα (Rxra) knockout mice revealed that loss of function in young mice caused delayed myelin debris uptake and slowed remyelination after experimentally-induced demyelination. Alternatively, retinoid X receptor agonists partially restored myelin debris phagocytosis in aged macrophages. The agonist bexarotene, when used in concentrations achievable in human subjects, caused a reversion of the gene expression profile in multiple sclerosis patient monocytes to a more youthful profile and enhanced myelin debris phagocytosis by patient cells. These results reveal the retinoid X receptor pathway as a positive regulator of myelin debris clearance and a key player in the age-related decline in remyelination that may be targeted by available or newly-developed therapeutics.

Clinical outcome following pneumonectomy for management of chronic pyothorax in four cats.

Pneumonectomy is the resection of all lung lobes from one side of the thorax. The clinical findings, treatment and outcome of four cases of feline chronic pyothorax managed with exploratory thoracotomy and pneumonectomy are reported. All cases were initially medically managed with thoracic drain placement and antibiosis. However, resolution was not achieved with medical therapy and diagnostic imaging findings consistent with an area of abscessation or marked lung lobe consolidation were identified, supporting a decision for surgical management. Surgical exploration was performed via median sternotomy and, on the basis of gross inspection, non-functional lung was removed. A left-sided pneumonectomy was performed in three cats and a right-sided pneumonectomy in one. All cases survived to discharge and an excellent quality of life was reported on long-term follow-up. Pneumonectomy appears to be well tolerated in the cat.