Bruno Benetti Junta Torres

Clinical risk factors associated with anti-epileptic drug responsiveness in canine epilepsy.

The nature and occurrence of remission, and conversely, pharmacoresistance following epilepsy treatment is still not fully understood in human or veterinary medicine. As such, predicting which patients will have good or poor treatment outcomes is imprecise, impeding patient management. In the present study, we use a naturally occurring animal model of pharmacoresistant epilepsy to investigate clinical risk factors associated with treatment outcome. Dogs with idiopathic epilepsy, for which no underlying cause was identified, were treated at a canine epilepsy clinic and monitored following discharge from a small animal referral hospital. Clinical data was gained via standardised owner questionnaires and longitudinal follow up data was gained via telephone interview with the dogs’ owners. At follow up, 14% of treated dogs were in seizure-free remission. Dogs that did not achieve remission were more likely to be male, and to have previously experienced cluster seizures. Seizure frequency or the total number of seizures prior to treatment were not significant predictors of pharmacoresistance, demonstrating that seizure density, that is, the temporal pattern of seizure activity, is a more influential predictor of pharmacoresistance. These results are in line with clinical studies of human epilepsy, and experimental rodent models of epilepsy, that patients experiencing episodes of high seizure density (cluster seizures), not just a high seizure frequency pre-treatment, are at an increased risk of drug-refractoriness. These data provide further evidence that the dog could be a useful naturally occurring epilepsy model in the study of pharmacoresistant epilepsy.

Effects of dantrolene on apoptosis and immunohistochemical expression of NeuN in the spinal cord after traumatic injury in rats

Dantrolene has been shown to be neuroprotective by reducing neuronal apoptosis after brain injury in several animal models of neurological disorders. In this study, we investigated the effects of dantrolene on experimental spinal cord injury (SCI). Forty‐six male Wistar rats were laminectomized at T13 and divided in six groups: GI (n = 7) underwent SCI with placebo and was euthanized after 32 h; GII (n = 7) underwent laminectomy alone with placebo and was euthanized after 32 h; GIII (n = 8) underwent SCI with dantrolene and was euthanized after 32 h; GIV (n = 8) underwent SCI with placebo and was euthanized after 8 days; GV (n = 8) underwent laminectomy alone with placebo and was euthanized after 8 days; and GVI (n = 8) underwent SCI with dantrolene and was euthanized after 8 days. A compressive trauma was performed to induce SCI. After euthanasia, the spinal cord was evaluated using light microscopy, TUNEL staining and immunochemistry with anti‐Caspase‐3 and anti‐NeuN. Animals treated with dantrolene showed a smaller number of TUNEL‐positive and caspase‐3‐positive cells and a larger number of NeuN‐positive neurons, both at 32 h and 8 days (P ≤ 0.05). These results showed that dantrolene protects spinal cord tissue after traumatic SCI by decreasing apoptotic cell death.

Responses to successive anti-epileptic drugs in canine idiopathic epilepsy

Pharmacoresistance to anti-epileptic drugs (AEDs) can be a source of frustration for owners and veterinarians alike in the treatment of canine idiopathic epilepsy (IE), with ongoing seizures having a significant negative impact upon the quality of life of affected dogs and owners (Chang and others 2006, Wessmann and others 2014). Finding an effective AED that reduces seizure frequency to an acceptable level (generally classed as more than 50 per cent reduction in veterinary medicine), or results in remission (seizure-freedom) can be a long process, with several AEDs trialled before optimum treatment is reached (Packer and others 2014). With more AEDs becoming available to veterinary patients, knowing whether (and when) to include further therapies can be challenging for practitioners, when faced with the balance between seizure control and side effect profiles. In human epilepsy, response rates to first-line and further AEDs have been studied in several populations, with the probability of seizure control diminishing progressively with successive AED treatments. Kwan and Brodie (2000) reported response rates (as a proportion of the population) of 47, 13 and 4 per cent for first-line, second-line and third-line drugs, respectively (Kwan and Brodie 2000). Similarly, Mohanraj and Brodie (2006) reported response rates of 50.4, 10.7 and 2.3 per cent, respectively, with just 0.8 per cent responding to any further drugs (Mohanraj and Brodie 2006). If the initial AED fails to control seizures, the prognosis for seizure control may be poor. Failure to respond to the first AED has been demonstrated to predict becoming refractory at two-year follow-up in a study of children with temporal lobe epilepsy (Dlugos and others 2001). In a further study, of those patients unresponsive to the first AED, 76 per cent failed two or more AEDs and 38 per cent failed at least four (Perucca and others 2011). These …

Modelo experimental de trauma medular agudo produzido por aparelho estereotáxico modificado

Foram utilizados 55 ratos machos da especie Rattus novergicus, variedade Wistar, com o objetivo de propor um modelo experimental de trauma medular produzido por aparelho estereotaxico modificado, capaz de reproduzir clinicamente lesoes medulares padronizadas. Apos realizacao de laminectomia dorsal de T13, utilizou-se peso compressivo de 50,5g (25 animais - grupo I) ou 70,5g (30 animais - grupo II), durante cinco minutos, comprimindo a medula espinhal. Os animais foram assistidos durante oito dias, por meio de testes comportamentais para avaliar a sensibilidade dolorosa, a capacidade motora, o posicionamento tatil e proprioceptivo e a capacidade de manter-se em plano inclinado. No grupo I, observaram-se deficits neurologicos moderados e transitorios, que variaram entre os animais. No grupo II, foi possivel obter um trauma padronizado, caracterizado por paraplegia bilateral e simetrica dos membros posteriores, perda de propriocepcao e da sensibilidade dolorosa de todos os animais. A utilizacao do aparelho estereotaxico desenvolvido permite reproduzir clinicamente trauma medular padronizado em ratos, de maneira simples, economica e satisfatoria, o que podera proporcionar avancos nas investigacoes terapeuticas, abrangendo doencas neurodegenerativas, como e o caso do trauma medular agudo.

The ameliorating effect of dantrolene on the morphology of urinary bladder in spinal cord injured rats

In animal models of spinal cord injury (SCI), the urinary bladder can undergo significant structural and physiological alterations. Dantrolene has been shown to be neuroprotective by reducing neuronal apoptosis after SCI. Furthermore, in addition to its anti-inflammatory and antioxidant properties, it appears to have a beneficial action on voiding, once this drug acts on the external urethral sphincter relaxation. In the present study, we investigated the effects of dantrolene on urinary bladder injury that follows experimental SCI. Forty-six male Wistar rats were laminectomized at T13, and a compressive trauma was performed to induce SCI. After euthanasia, the urinary bladder was removed for gross and histological evaluation. Traumatized animals showed urinary retention with severe hemorrhagic cystitis. Injured animals treated with dantrolene had less bladder hemorrhage and inflammatory infiltrate than those treated with placebo (p<0.05). Our results demonstrate that dantrolene may protect against urinary bladder lesions that follow SCI. Treating spinal cord-injured patients with this agent may be a promising additional therapeutic strategy to alleviate the accompanying inflammatory process. The results of the current study show that dantrolene has protective effects on spinal cord contusion-induced urinary bladder injury. The impaired integrity of bladder morphology was ameliorated by dantrolene treatment.

Risk factors for cluster seizures in canine idiopathic epilepsy

Cluster seizures (CS), two or more seizures within a 24-hour period, are reported in 38-77% of dogs with idiopathic epilepsy (IE). Negative outcomes associated with CS include a reduced likelihood of achieving seizure freedom, decreased survival time and increased likelihood of euthanasia. Previous studies have found factors including breed, sex and neuter status are associated with CS in dogs with IE; however, only one UK study in a multi-breed study of CS in IE patients exists to the authors knowledge, and thus further data is required to confirm these results. Data from 384 dogs treated at a multi-breed canine specific epilepsy clinic were retrospectively collected from electronic patient records. 384 dogs were included in the study, of which nearly half had a history of CS (49.1%). Dogs with a history of CS had a younger age at onset than those without (p = 0.033). In a multivariate model, three variables predicted risk of CS: a history of status epilepticus (p = 0.047), age at seizure onset (p = 0.066) and breed (German Shepherd Dog) (p < 0.001). Dogs with a history of status epilepticus and dogs with an older age at seizure onset were less likely to be affected by cluster seizures. German Shepherd Dogs (71% experiencing CS) were significantly more likely to suffer from CS compared to Labrador Retrievers (25%) (p < 0.001). There was no association between sex, neuter status, body size and CS. Further studies into the pathophysiology and genetics of CS are required to further understand this phenomenon.

Association of riluzole and dantrolene improves significant recovery after acute spinal cord injury in rats

BACKGROUND CONTEXT Damage to the spinal cord can result in irreversible impairment or complete loss of motor, sensory, and autonomic functions. Riluzole and dantrolene have been shown to provide neuroprotection by reducing neuronal apoptosis after brain and spinal cord injury (SCI) in several animal models of neurologic disorders. As these drugs protect the injured spinal cord through different mechanisms, we investigated the cumulative effects of riluzole and dantrolene. PURPOSE This study aimed to investigate the neuroprotective efficacy of the combined administration of riluzole and dantrolene in experimental thoracic SCI. STUDY DESIGN Twenty-nine Wistar rats were laminectomized at T12 and divided in five groups. Rats in GI (n=6) underwent laminectomy alone and were treated with placebo. Rats in GII (n=6) underwent laminectomy followed by SCI and were treated with placebo. Rats in GIII (n=5) underwent laminectomy followed by SCI and were treated with riluzole and placebo 15 minutes and 1 hour after laminectomy, respectively. Rats in GIV (n=6) underwent laminectomy followed by SCI and were treated with placebo and dantrolene 15 minutes and 1 hour after laminectomy, respectively. Rats in GV (n=6) underwent laminectomy followed by SCI and were treated with riluzole and dantrolene 15 minutes and 1 hour after laminectomy, respectively. A compressive trauma was performed to induce SCI. METHODS Behavioral testing of hind limb function was performed using the Basso Beattie Bresnahan locomotor rating scale, which revealed significant recovery in the group treated with the association of riluzole and dantrolene compared with other groups. After euthanasia, the spinal cord was evaluated using light microscopy and immunochemistry with anti-NeuN and transferase dUTP nick-end-labeling (TUNEL) staining. RESULTS Animals treated with the association of riluzole and dantrolene showed a larger number of NeuN-positive neurons adjacent to the epicenter of injury (p≤.05). Furthermore, the TUNEL staining was similar between animals treated with riluzole and dantrolene and those that did not receive spinal cord trauma (p>.05). CONCLUSIONS These results showed that riluzole and dantrolene have a synergistic effect in neuroprotection after traumatic SCI by decreasing apoptotic cell death.

Fixação esquelética externa em fratura tarsometatársica de seriema (Cariama cristata): relato de caso

An adult red-legged seriema (Cariama cristata) was referred for examination with history of trauma by capture. The physical examination revealed lameness in the right pelvic limb, sensibility to touch and open fracture of tarsumetatarsus. The treatment was done with surgical closed reduction using a external skeletal fixator type II with acrylic connecting bar. The surgical technique applied was satisfactory for the treatment of the fracture of tarsumetatarsus, since there was bone healing and functional return of the limb at 60 days after surgery.

Clinical and pathological aspects of multicentric hemangiosarcoma in a Pinscher dog

A 3-year-old female Pinscher dog was presented with a history of lameness and pain in hind limbs for one week which acutely progressed to non-ambulatory paraparesis. The dog had been apathetic and anorexic during the six days prior to presentation. The neurological findings were compatible with upper motor neuron signs to the left hind limb due to a spinal cord compressive mass on the twelfth thoracic vertebral body. On the other hand, signs of lower motor neurons to the right hind limb were due to a mass with a pathological fracture in the right proximal femur, compressing the sciatic nerve. A histopathological analysis of all organs revealedthe proliferation of endothelial cells showingin filtrative growth and organization into vascular structures with a solid pattern. In addition, immunohistochemycal analysis revealed low proliferation index and citoplasmatic positivity for CD-31, confirming the vascular nature of the neoplasm. Clinical, histopathological and immunophenotipical findings were consistent with hemangiosarcoma.

Key-Gaskell syndrome in Brazil: first case report

Feline dysautonomia is a devastating disease characterized by neuronal degeneration in autonomic ganglia that results in clinical signs related to dysfunction of the sympathetic and parasympathetic nervous systems. The cause is unknown and this disease has a poor prognosis and no definitive treatment. Most reports have been described in few countries around the world, but the prevalence may be underestimated in countries like Brazil. This study describes the progression and clinicopathological changes of dysautonomia in a 17-month-old female Brazilian shorthair cat.