Sparing the gut: COX-2 inhibitors herald a new era for treatment of horses with surgical colic.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage a wide variety of conditions in horses, including management of colic. Flunixin meglumine is by far the most commonly used drug in the control of colic pain and inflammation and has become a go-to for not only veterinarians but also horse-owners and nonmedical equine professionals. NSAID use, however, has always been controversial in critical cases due to a high risk of adverse effects associated with their potent cyclo-oxygenase (COX) inhibition. There are two important COX isoenzymes: COX-1 is generally beneficial for normal renal and gastrointestinal functions and COX-2 is associated with the pain and inflammation of disease. Newer selective NSAIDs can target COX-2-driven pathology while sparing important COX-1-driven physiology, which is of critical importance in horses with severe gastrointestinal disease. Emerging research suggests that firocoxib, a COX-2-selective NSAID labelled for use in horses, may be preferable for use in colic cases in spite of the decades-long dogma that flunixin saves lives.

Multicentre, blinded, randomised clinical trial comparing the use of flunixin meglumine with firocoxib in horses with small intestinal strangulating obstruction.

BACKGROUND: Small intestinal strangulating obstruction (SISO) is associated with endotoxaemia which leads to an increased risk of death. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat signs of endotoxaemia by inhibiting cyclo-oxygenases (COX). COX-1 is expressed constitutively and promotes gut barrier function, whereas COX-2 is inducible and contributes to the signs of endotoxaemia. In preclinical SISO trials, intestinal barrier recovery was more complete with reductions in endotoxin permeability in horses treated with COX-2 selective NSAIDs as compared with horses treated with flunixin meglumine. OBJECTIVES: We hypothesised that treatment of post-surgical SISO horses with firocoxib (COX-2 selective) would reduce the signs of endotoxaemia to a greater extent than flunixin meglumine (nonselective COX inhibitor) while continuing to provide similar levels of pain control. STUDY DESIGN: Blinded randomised clinical trial. METHODS: In addition to clinical monitoring, preoperative and 12-, 24- and 48-h post-operative plasma samples were assessed for prostaglandin E2 (PGE2 ), thromboxane B2 (TXB2 ), TNF⍺ and soluble CD14 (sCD14). RESULTS: In 56 recruited SISO horses, either flunixin meglumine (1.1 mg/kg, i.v., q12h) or firocoxib (0.3 mg/kg, i.v. loading dose; 0.1 mg/kg, i.v., q24h) was given in the post-operative period in three university hospitals from 2015 to 2017. COX-2 selectivity was confirmed by a relative lack of inhibition of the COX-1 prostanoid TXB2 by firocoxib and significant inhibition by flunixin meglumine (P = 0.014). Both drugs inhibited the COX-2 prostanoid PGE2 . There were no significant differences in pain scores between groups (P = 0.2). However, there was a 3.23-fold increased risk (P = 0.04) of increased plasma sCD14 in horses treated with flunixin meglumine, a validated biomarker of equine endotoxaemia. MAIN LIMITATIONS: Horses were all treated with flunixin meglumine prior to referral. In addition, many horses were treated with lidocaine, which has been shown to mitigate the deleterious effects of flunixin meglumine. CONCLUSIONS: In SISO cases, firocoxib reduced a biomarker of endotoxaemia as compared with flunixin meglumine while continuing to provide similar levels of pain control.

Impaired intestinal barrier function and relapsing digestive disease: Lessons from a porcine model of early life stress.

Within this issue of Neurogastroenterology and Motility, an article by Pohl et al highlights new insights from a powerful porcine model of the link between early life adversity and relapsing functional gastrointestinal disorders. Early weaning stress closely mimics the early life psychosocial stressors that have been linked to adult onset gastrointestinal dysfunction. This early weaning model provides reproducible and highly translatable outcomes in young stress-challenged pigs. Due to the convincingly comparable neurological and gastroenterological anatomy and physiology between pigs and human beings, gastrointestinal stress and injury studies utilizing swine models will provide invaluable insights to improve our understanding and treatment of gastrointestinal disease in human beings. Future studies to examine mechanisms underlying this link between early life adversity and functional gastrointestinal disorders will explore the roles of gender and hypomaturity in gastrointestinal responses to stress.

Hypothalamic hamartoma, precocious puberty and gelastic seizures: a special model of "epileptic" developmental disorder.

Based on a review of the literature and a detailed longitudinal single case study of a child with early onset gelastic seizures and hypothalamic hamartoma, the authors review the arguments suggesting that the acquired cognitive and behavioral symptoms seen in the majority of cases of this special epileptic syndrome result from a direct effect of the seizures. The early neurobehavioral profile of the case presented in this paper and that of a previous study is particular and combines features of a pervasive developmental and an attention deficit disorder which are probably closely related to the particular location of the epilepsy and its spread from the hypothalamus.

[So-called benign epilepsies in children]. / Epilepsies dites "bénignes" de l'enfant.

This paper reviews the concept of "benign" childhood epilepsies on the basis of the literature review and our own published work. The practical diagnostic, prognostic and therapeutic implications of this concept and its limits are discussed and the main syndromes reported as "benign" are reviewed. The recognition of some childhood epileptic syndromes whose prognosis can be established from the onset of the disorder has proven very useful, but does not apply, by far, to all epileptic children. Other important informations on the natural history of various epilepsies, the knowledge of general favorable prognostic factors and the low relapse rate after drug withdrawal in many successfully treated cases has greatly helped the clinical management of many situations. There are numerous myths surrounding the diagnosis "epilepsy" which can have deleterious psychological consequences and which are important to recognize and fight. A globally "benign" final prognosis will depend as much on these factors as on the absolute number of seizures, the duration of the disease and the need for medical treatment.

[Epilepsy and accidents: what is the risk in children?]. / Epilepsie et accidents: quel risque chez l'enfant?

BACKGROUND: Constant distress and overprotection of parents result from the apprehension and misinformation received, regarding epilepsy of their children and the risk of accidents occurring due to a seizure. Large retrospective studies show that the epileptic children are not more often concerned than the general population. CASE REPORTS: One hundred and ninety-eight epileptic children without permanent motor or mental handicap were followed between 1971 and 1981, covering 1056 years of child's life. They were compared to 3822 injured children admitted to the surgical pediatric emergency unit between 1983 and 1992. RESULTS: Only six accidents occurred because of a seizure in the first group of epileptic children. There were neither deaths nor sequelae. Four of these six accidents revealed an unknown epilepsy. Among the 3,822 injured children, 19 were epileptic but only four of these 19 accidents were caused by a seizure. There were no sequelae. CONCLUSION: The majority of epileptic children without associated handicap are able to have all the normal activities of healthy children. Only severe epilepsies with frequent refractory seizures, some reflex epilepsies and some cases before the seizures are under control require constant supervision.

Autistic regression in relation to limbic pathology and epilepsy: report of two cases.

The authors report a follow-up study of two boys who presented with autistic regression (after normal early development) at 13 and 22 months. Both were found on cerebral imaging to have tuberous sclerosis, with lesions involving the limbic system, bilaterally in the second child. The first child's regression coincided with the onset of partial complex seizures; disappearance of the autistic behaviour and marked improvement in cognitive development occurred with remission of the epilepsy. The second child, who had probable seizures and a late-appearing epileptic focus on EEG, remained severely disabled. The autistic behaviour appears to be linked to pathology in the limbic system and a direct role of epilepsy in the regression is proposed.

Transient idiopathic dystonia in infancy.

The authors report eight otherwise normal children who presented with transient dystonic postures and/or movements in infancy. The anomalies appeared during the first months of life, progressed during a period then gradually disappeared at follow-up (from 3 months to 5 years). Differential diagnosis with primary orthopedic problems, cerebral palsy and early progressive CNS disease may be difficult at onset of the symptoms. Transient dystonia is probably one of the numerous mechanisms responsible for some abnormalities of tone, posture and movement in infancy and may account for some of the cases labeled as "transient cerebral palsy". Our cases resemble those described by Willemse (19) as "benign idiopathic dystonia in the first year of life".

Hidden intelligence of a multiply handicapped child with Joubert syndrome.

A child with Joubert syndrome (episodic hyperpnoea, abnormal eye-movements and ataxia) was followed from birth to eight years of age. Although severe mental retardation was suspected until approximately five years of age, unexpected and exceptional mental capacities were evident at later follow-up. Adequate testing and appropriate stimulation of children with such a severe early motor disorder are difficult, so they may give a false impression of mental retardation. The history of this child challenges the notion that mental retardation is part of Joubert syndrome.

Adult follow-up of the acquired aphasia-epilepsy syndrome in childhood. Report of 7 cases.

The authors report at adult age 7 patients (6 men, one woman) with the syndrome of "acquired aphasia-epilepsy", 6 of which had been previously studied as children. The results of the language, neuropsychological and socio-educational evaluation detailed many years after the onset of the aphasia are the subject of this report. One man has recovered completely, one has a normal oral language but is severely dyslexic, one has recovered normal comprehension but has severe expressive language problems. Four have absent language comprehension and lack of expressive speech, and only one of them has learned and is using sign language with some efficiency. None has developed functional written language. Attempts to offer a substitutive language to children with prolonged inability to understand and use oral language appears important but is fraught with problems. Although there are no conclusive data about the role of the continuous paroxysmal EEG discharges and the effect of their suppression with drug treatment on the prognosis of the aphasia, the definite fluctuations of the aphasia in some cases, the isolated recent case reports of definitive improvement with drug treatment justify further trials in this potentially severe and chronic condition.

Combined myoclonic-astatic and "benign" focal epilepsy of childhood ("atypical benign partial epilepsy of childhood"). A separate syndrome?

The authors have followed six children with atypical epilepsies but a favorable evolution, consisting in minor motor seizures of the myoclonic-astatic type (with diffuse slow spike-waves on the electroencephalogram) together with clinical and EEG features seen in benign focal epilepsy of childhood (BFEC), an association recently reported by Aicardi and Chevrie (1982). The maintenance of a normal neurological function despite severe epilepsy, the absence of tonic seizures and the marked activation of the spike discharges during sleep were described by these authors as important characteristics suggesting a good prognosis. The purpose of this study was to see if these children indeed represent a particular subgroup of idiopathic epilepsy and to draw attention to a special clinical and EEG combination indicating a possibly favorable ultimate outcome, in children usually diagnosed as suffering from Lennox-Gastaut syndrome. The six cases closely resembled the group described by Aicardi and Chevrie (1982), although the clinical and EEG features of BFEC were not as striking as in their cases. Also transient mental deterioration occurred during the active seizure periods. The therapeutic benefit of the various drugs tried was difficult to assess, but the behavior was often perturbed by medication. Although it is not possible to decide at the present time if these cases represent a particular epileptic syndrome, the special combination of clinical and EEG features seems characteristic enough to justify prospective studies of similar cases in the future.

Partial epilepsy in neurologically normal children: clinical syndromes and prognosis.

A clinical and electroencephalographic study of 107 neurologically normal children with partial seizures was undertaken to verify the existence and determine the frequency of epileptic syndromes reported in selected populations. Sixty-three children had simple partial seizures, 39 had complex partial seizures, and 5 children were unclassifiable. The syndrome of benign partial epilepsy of children with rolandic spikes (BPEC, 38 cases) was clearly identified and its uniformly benign final prognosis was confirmed even if some of these children had at times severe or poorly controlled seizures. Among the children with simple partial seizures outside the BPEC (25 cases) and complex partial seizures (39 cases), no homogeneous clinical or electroclinical subgroup could be found. Two children with benign partial epilepsy and myoclonic-astatic seizures ("atypical benign partial epilepsy of childhood") and one child with "benign epilepsy with occipital spike-waves" were identified. 74% of children with epilepsy with complex partial seizures (ECP) had a 1-year seizure-free interval, and many children with epilepsy with simple partial seizures outside the BPEC group (ESP) had no more than two seizures. A benign course is thus not limited to the BPEC but is difficult to predict. Prospective studies are necessary to confirm the existence of well-defined benign syndromes among the idiopathic partial epilepsies of childhood, which appear quite rare outside the BPEC.

Paroxysmal visual disturbances of epileptic origin and occipital epilepsy in children.

A special form of partial occipital epilepsy clinically resembling migraine and possibly related to the benign focal epilepsies of childhood has recently attracted attention (Gastaut 1982) but its existence is still debated. To approach this problem, in a group of 195 children with idiopathic partial or generalized epilepsy we have studied those who had visual complaints as part of their seizures (twelve children) and those who also had migraine (four children). The clinical and electroencephalographic features of these children were analyzed together with those of another group of thirty children diagnosed as migraine accompagnée in which an EEG had been obtained (3/30, i.e. 10% had paroxysmal spike-waves: one centrotemporal focus, two generalized spike-waves). One child with the type of epilepsy described by Gastaut (1982) as partial benign occipital epilepsy (phosphenes, moving lights, headaches and occipital high voltage biphasic spike-waves blocked by eye opening on the EEG) was found in the epileptic group whereas the other children of this group, including those with associated migraine, had other types of epilepsy. This "new" type of epileptic syndrome can be distinguished from symptomatically resembling entities but its place needs to be further defined.

[Cerebral distress in full-term newborns: method of early prognosis of the quality of long-term survival]. / Détresse cérébrale du nouveau-né à terme: méthode de pronostic précoce quant à la qualité de la survie à long terme.

A study on 122 full-term newborns with cerebral distress has given the basis for a mathematical model allowing to calculate the risk of poor evolution due to neurological disorders occurring in the first week of life. For each patient a score on his neurological status is established at 3 or 7 days of age. Only four essential neurological characteristics have to be considered: primary reflexes, convulsions, apathy or swallowing disorders, respiratory disorders. All possible score combinations are listed, and each of them is associated with a risk factor (in percent) for poor evolution. A long-term prognosis can therefore be obtained by simple clinical observation, making a score and consulting the list.

Cerebral distress in full-term newborns and its prognostic value. A follow-up study of 90 infants.

The history of 90 full-term infants with neonatal cerebral distress was examined. Informations concerning pregnancy, delivery, neonatal status, clinical and laboratory evolution were compared with final outcome in each case. It was then possible to distinguish certain clinical features significantly associated with poor prognosis. After statistical analysis, different adverse criteria were selected, such as severe neonatal asphyxia, associated respiratory disorders, acute anemia, and especially neurological signs with regard to their chronology. This part of the study has resulted in a classification of the neurological signs and has permitted the description of both malignant and benign cerebral distress syndromes.