Canine and Feline Epilepsy. Luisa De Risio
4.1 and Chapters 12 and 24), fluid therapy to correct metabolic acidosis, convective whole body cooling (e.g. wetting the fur, fan) and respiratory support. General anaesthesia may be necessary in animals that do not respond to AEMs (see Chapter 24). After the acute clinical signs have been controlled, treatment must focus on minimizing possible liver damage in dogs.
Prognosis
Prognosis is generally good in animals treated promptly and aggressively. A retrospective study including 18 dogs with metaldehyde intoxication reported a recovery rate of 83% (Yas-Natan et al., 2007). Prognosis is guarded in animals presenting with severe hyper-thermia (>41.6°C or 107°F). Prolonged status epilepticus following metaldehyde intoxication has not been associated with spontaneous recurrent seizures in dogs (Jull et al., 2011). Recovery may take approximately 2 weeks in cats (Puschner, 2006).
Rodenticides
Strychnine
Overview
Strychnine has been used as pest control of rodents and other animal species worldwide. Its sale has been restricted or banned without special permits in several countries. However, malicious and less commonly accidental or secondary (from ingestion of strychnine-poisoned rodents) poisonings of companion animals still occurs (Berny et al., 2010). The toxic dose in most animals ranges from 0.3 to 1.0 mg/kg with the lethal dose being 2.0 mg/kg in cats.
Mechanism of action
Strychnine antagonizes stereochemically and competitively the motor inhibitory neuro-transmitter glycine at the brainstem and spinal cord level and inhibits glycine release from Renshaw cells. Some supraspinal signs may also be associated with strychnine inhibition of GABA.
Clinical presentation
Clinical signs generally occur within 10 min to 2 h after toxin ingestion and typically begin with nervousness and restlessness, rapidly progressing to increased tone of both extensor and flexor muscles resulting in a stiff gait. All skeletal muscles including the appendicular, epaxial, facial, abdominal and respiratory muscles have tetanic spasms. Auditory (e.g. loud noise), visual (e.g. bright light) and tactile stimuli exacerbate the tetanic muscle spasms and can trigger tonic seizures. This feature, however, is not specific to strychnine and has been observed in other types of poisonings including metaldehyde, penitrem A, roquefortine and chlorinated hydrocarbons. Hyperthermia (secondary to the severe muscle contractions) is commonly observed. The animal remains conscious during seizures unless respiratory paralysis occurs. Apnea can lead to cerebral anoxia, loss of consciousness and death 30 min to 2 h following the onset of neurologic signs, if the animal is untreated (Murphy, 2002).
Diagnosis
Baits may have specific colours in some countries, which can help recognition during gastric decontamination. Definitive diagnosis is based on toxicologic analysis of stomach contents, urine, blood or hepatic and renal tissue. Ante-mortem analysis of stomach contents and urine is most likely to provide a diagnosis. The dimethoxy derivative of strychnine, brucine (2,3-dimethoxystrychnidin-10-one), may be detected in serum.
Management
Treatment includes decontamination (induction of emesis in asymptomatic animals or gastric lavage followed by activated charcoal and cathartic administration in animals showing clinical signs of intoxication) (Table 4.1), promoting toxin excretion, controlling the tetany and seizures (Table 4.1, see Chapters 12 and 24), convective whole body cooling, adequate oxygenation (Murphy, 2002) and supportive care. Sedation or general anaesthesia for 24–72 h may be required. Forced diuresis with 5% mannitol in isotonic saline and acidification of the urine will enhance urinary elimination of strychnine. Animals with respiratory failure should be administered oxygen and if needed intubated and ventilated. Non-anesthetized animals should be kept in a dimly lit, quiet area and all forms of sensory stimulation should be minimized.
Prognosis
Prognosis is fair to guarded, depending on the amount of toxin ingested and promptness of treatment. If the animal survives the first 24 h post-toxin ingestion, prognosis for complete recovery is good.
Bromethalin
Overview
Bromethalin is a rodenticide that is sometimes implicated in accidental or malicious poisonings of small animals. It is available in pelleted forms such as place packs, blocks or bars of bait and baited worms (DeClementi and Sobczak, 2012). Exposure mainly occurs by ingestion of bromethalin bites. Secondary (or relay) poisoning may occasionally occur by ingestion of bromethalin-poisoned rodents. Bromethalin is readily absorbed from the gastrointestinal tract and reaches peak plasma levels within several hours after ingestion. It is highly lipophilic and therefore reaches high concentration in the brain.
Mechanism of action
Bromethalin and its active metabolite, desmethyl bromethalin, uncouple oxidative phosphorylation resulting in decreased cellular adenosine tri-phosphate (ATP) concentrations and reduced activity of ATP-dependent sodium and potassium ion channel pumps. This produces an increase in intracellular sodium concentrations, intracellular movement of water and consequent cerebral oedema, vacuolization of myelin and increased intracranial pressure.
Clinical presentation
Onset and type or clinical signs are dose-dependent. Dogs ingesting 2.5 to 5 mg/kg of bromethalin develop clinical signs in 1 to 4 days (Murphy, 2002), whereas dogs ingesting more than 5 mg/kg of bromethalin may develop clinical signs within 2–24 h after ingestion. Low doses (e.g. 2.5 mg/kg in dogs) result in pelvic limb ataxia and/or paresis/paralysis with extensor rigidity and obtunded mental status. High doses (e.g. 5 to 6.5 mg/kg in dogs) produce hyperexcitability, tremors, focal motor and generalized seizures, hyperthermia, obtunded mental status, which can progress to stupor, coma, decerebrate posture and death secondary to respiratory arrest (Dorman et al., 1990a, b). Cats ingesting 0.54 mg/kg develop signs (including ataxia, focal motor seizures, vocalization, obtunded mental status and stupor) 2 to 7 days after exposure (Dorman et al., 1990c). Most recently clinical signs and death have been reported following exposure to bromethalin doses as low as 0.46 mg/kg in dogs and 0.24 mg/kg in cats (DeClementi and Sobczak, 2012).
Diagnosis
The ante-mortem diagnosis is most often made based on the history of bait ingestion (stools may have a green discoloration) and the development of clinical signs. Definitive diagnosis can be reached only post-mortem by detecting bromethalin or its metabolites in kidney, liver, fat or brain samples using gas chromatography with electron capture (Dorman et al., 1990a, b). Samples should be submitted frozen and protected from light.
Management
There is no antidote to bromethalin. Treatment involves decontamination and prevention of further toxin adsorption (induction of emesis or gastric lavage followed by repeated administration of activated charcoal and administration of a cathartic with the