Inorganic Chemical Neurotoxicities

Lead Poisoning

Documentation of specific cases of naturally occurring lead poisoning in goats is rare in the contemporary veterinary lit­erature. Nevertheless, several reviews of goat diseases iden­tify lead poisoning as a disease of goats producing neurologic signs similar to those seen in affected cattle or sheep.

Goats are considered resistant to lead poisoning com­pared to cattle and dogs and have been observed not to become ill under circumstances where companion cattle show signs of disease. Whether this was caused by innate resistance or an unwillingness to consume sources of lead is not clear (Guss 1977). Certainly they are exposed to lead in certain circumstances, such as when they graze near lead-smelting operations, in which case elevated blood and tissue lead levels have been documented (Memon et al. 2014), along with depressed blood copper and cobalt levels in one study (Swarup et al. 2006). In countries where lead-containing petrol is still in use, goats grazing along roadsides can have substantially elevated blood and tissue lead levels. In an Indian study, goats grazing near highly trafficked roads had milk lead levels of 4.6 ppm or greater, whereas the US Food and Drug Administration’s accepta­ble level for lead in milk is 0.3 ppm (Bhatia and Choudhri 1996).

At least experimentally, goats refused to eat lead-based paint or pure lead acetate, despite the sweet taste of the lat­ter (Davis et al.

Diagnosis of lead poisoning in goats depends on a strong history of exposure, identification of the source, and con­firmation of increased blood or tissue lead levels. Goats appear to accumulate lead less dramatically than other spe­cies. Experimentally poisoned, clinically ill goats had whole blood lead levels as low as 0.2 ppm, liver levels as low as 5.5 ppm, and renal cortex levels as low as 26 ppm. Values higher than these should be considered indicative of lead poisoning when evaluating field cases. Liver lead levels in aborted fetuses greater than 1.5 ppm are sugges­tive of lead-induced abortion. It has also been reported that blood porphyrin levels are reliably elevated in lead poison­ing in goats. Goats experimentally administered lead ace­tate for 91 days had progressively increasing mean blood porphyrin levels in the range of 31.7-56.9 μg∕dL, while control goats had levels in the range of 23.5-24.6 μg∕ dL. Most of the lead-exposed goats also showed a so-called lead line in radiographs of forelimbs, with marked radio­paque bands at the distal metaphysis of the radii, indicat­ing incorporation of lead in bone at the growth plates. The goats were 8-9 months old at the onset of the exposure (Swarup et al. 1990).

Because the occurrence of nervous signs in lead poison­ing of goats is not firmly established, veterinarians are strongly encouraged to submit whole blood for lead analy­sis in all suspect cases, and to pursue alternate diagnoses while waiting for test results. When blindness is present in conjunction with other neurologic signs, serious consider­ation must be given to PEM as an alternate diagnosis and thiamine therapy at 10 mg∕kg should be instituted immedi­ately. While IV administration of thiamine is often sug­gested, there are anecdotal reports of death in goats using this route, so if given IV it must be given slowly, or prefer­ably given IM or SC.

When lead poisoning is the working diagnosis, it is important to identify the source. If the lead was ingested, it may be necessary to perform a rumenotomy to remove ingested lead that may be present, or to use cathartics such as magnesium sulfate (400 mg/kg, given orally) to flush out the digestive system. Otherwise, lead may continue to be absorbed from the gut despite other therapeutic interven­tions, and this will be reflected in persistent high blood lead levels.

Treatment is similar to that of other species and is tar­geted primarily at chelation of lead for removal from the body. The chelating agent calcium disodium versanate remains the standard treatment in ruminants (Cebra and Cebra 2004). The recommended dosage is 110 mg/kg bw divided into two treatments, given IV at a six-hour interval and repeated for three to five days. After two days of rest, this can be repeated for an additional three to five days if needed. Treatment with calcium disodium versanate can be nephrotoxic, so patients should be kept well hydrated and monitored for evidence of kidney problems.

Another chelating agent that is used to treat lead poison­ing in humans is succimer (meso-2,3-dimercaptosuccinic acid), which has shown promise as a chelation treatment for lead removal in calves at a dose of 25 mg/kg adminis­tered IV once daily for four consecutive days (Meldrum and Ko 2003). As an adjunct to chelation therapy, adminis­tration of thiamine hydrochloride in cattle with lead poi­soning improved the clinical response. It resulted in better remission of nervous signs and also appeared to enhance the reduction of blood lead concentration (Coppock et al. 1991). The dose was 2 mg/kg bw thiamine hydrochlo­ride given IM once daily.

When lead poisoning is diagnosed in animals, careful investigation of the environment is warranted to identify and eliminate sources of exposure such as batteries, lead­based paints, putty, and contaminated forages, or, when the source itself cannot be eliminated, to remove animals from exposure. There is no information available concerning meat or milk withdrawal times following chelation therapy and as a matter of precaution, meat and milk from animals that have been confirmed with a diagnosis of lead poison­ing should not be used for human consumption.

Salt Poisoning

Salt poisoning occurs in livestock when there is excessive salt intake from the feed, inadequate water intake in the face of normal salt intake, or when only saline drinking water is available. The condition is most common in swine, but is also reported in cattle and sheep. Documentation of the condition in goats is rare, but it is sometimes included in discussions of diseases showing nervous signs (Guss 1977; Baxendell 1988).

In a case report from Italy, one of eight affected goats pre­sented with convulsions, opisthotonos, and respiratory dis­tress, while the other seven showed weakness and intense thirst. The severely affected goat died and had cerebral edema at necropsy. The others were successfully rehy­drated (Buronfosse 2000). Two outbreaks of salt poisoning in goats were reported from Brazil, both associated with provision of excessive salt in feed supplements in combina­tion with inadequate access to water (Duarte et al. 2019). The most frequent clinical signs were increased thirst, fre­quent urination, head lowering, head tilt, muscle weak­ness, mydriasis, and ataxia. Three of twelve affected animals died, but the others were successfully treated with dexamethasone, thiamine, and gradual return of access to water. Despite the intense thirst observed, rehydration of hypernatremic animals should be done slowly to prevent iatrogenic cerebral edema, preferably over 48-72 hours.

Signs of acute salt intoxication in other species include tremors, blindness, nystagmus, weakness, incoordination, knuckling of the fetlocks, head pressing, opisthotonos, convulsions, coma, and death associated with cerebral edema. When the disease occurs from a large dose of excess salt, signs of gastrointestinal irritation including vomiting, diarrhea, and abdominal pain may also be seen.

For all affected animals, a primary goal of treatment is to slowly return the animal to normal water and electrolyte balance over two to three days. It is cautioned that quickly lowering the serum sodium concentration will increase the osmotic gradient between the serum and the brain, with water following the gradient into the brain and increasing the likelihood of severe cerebral edema (Thompson 2016), and it is recommended that sodium serum concentration be monitored from the onset of treatment, with the goal of reducing the concentration at a rate of rate of 0.5-1 mEq/ L/h.

Bromide Intoxication

Two separate incidents of bromide poisoning of goats have been reported in the United States. One involved contami­nation of pastures by sodium bromide from an adjacent chemical dump, and the other contamination of oat hay grown on fields initially treated with methyl bromide as a nematocide (Knight and Costner 1977; Liggett et al. 1985). Although the latter source of bromide is organic, toxicity is believed to be caused by release and uptake by plants of bromide ion from the treated soil. The clinical signs were similar in both cases and developed over a period of days to weeks after exposure. Weakness and locomotor impair­ment were characteristic, with difficulty standing and turning, stumbling, and dragging of the feet while walking. Dribbling of urine; drooping ears, eyelids, and tail; and a progressive somnolence and recumbency were observed. Deaths occurred in both outbreaks.

Measurement of serum bromide can be diagnostic. In the sodium bromide-related outbreak, unexposed control goats had concentrations less than 0.625 mEq/L, exposed goats with no clinical signs measured 1.6-3.2 mEq/L, and clinically affected goats had concentrations more than 21.1 mEq/L. When laboratory measurement of serum chlo­ride is performed using an ion-selective electrode, pseuod- hyperchloremia may be recorded in animals with bromide poisoning.

There are no definitive necropsy lesions, although necro­sis of the ventral horn of the lumbar spinal cord was noted in one goat. There is no specific therapy reported, but some goats did recover after hospitalization with supportive care for 4-15 days.

Boron or Borax Intoxication

Borax may be found on the farm for use as a soil sterilant or fly control compound. Goats may be accidentally exposed, but are unlikely to voluntarily ingest it unless it was accidentally incorporated into the feed. Clinical signs of intoxication may include diarrhea, dehydration, and con­vulsions, before coma and death (Guss 1977).

The toxicity of boron has been demonstrated experimen­tally in goats (Sisk et al. 1988). A goat given sodium borate fertilizer orally at a dose of 3.6 g/kg bw exhibited signs of weakness and somnolence, with the chin resting on the floor. It developed muscle tremors and pasty feces, and died quietly eight hours after challenge. A second goat given the fertilizer at a dose of 1.8 g/kg did not become ill. Neurotoxicity is presumed to be involved in boron toxicity, but the mechanism is not fully known. A stimulatory effect on serotonergic and dopaminergic neurons has been pro­posed based on increased metabolites of serotonin and dopamine in CSF fluid of experimentally challenged goats (Sisk et al. 1990). No specific treatment is reported, but efforts to restore hydration may be helpful.