Neurotoxins: Clinical Manifestations & Treatment
ACVIM 2008
Sofia Cerda-Gonzalez, DVM, DACVIM (Neurology)
Ithaca, NY, USA


Toxins affecting the central, peripheral, or autonomic nervous systems are a diverse group of substances with one of the widest ranges of clinical manifestations. Although they can be categorized according to their most prominent effects, there is substantial crossover in their clinical manifestations. In the veterinary field patients generally present later than human their human counterparts, which may influence both clinical signs seen and recommendations for treatment, as discussed below.

Mechanism of Action

The specific methods by which neurotoxins exert their effects on the central and/or peripheral nervous system vary, and are not fully defined for all agents. Many neurotoxins do so by altering neuronal function. Excitatory neurotoxins commonly interfere with inhibitory neurotransmitter activity (in particular GABA and/or glycine) or enhance the function of excitatory neurotransmitters (such as glutamine, ACh), while central nervous system depressants act in an opposing way (ex: enhance GABA function). Neurotoxins may also modify neuronal activity by altering sodium, potassium, or calcium channel function or by interfering with normal cellular metabolism within the central nervous system. Lastly, clinical signs seen may be the result of damage to the central nervous system caused by a toxic agent or its metabolites (e.g., ethylene glycol toxicity).

Table 1. Source of small animal exposure to common toxins and their predominant effects on the nervous system.


Source of toxin

Overall nervous system effects


Caffeine, chocolate (theobromine)

Excitatory, CNS*


Snail bait

Excitatory, CNS

Pyrethrin / pyrethroids

Insecticides, parasiticides

Excitatory, CNS

Tremorgenic mycotoxins

Moldy dairy / prepared foods, moldy walnuts, garbage

Excitatory, CNS, PNS

Lead poisoning

Ceramic glaze, environment, paint, battery, toys

Excitatory, CNS; may interfere with PNS* function



Excitatory, CNS (brain, spinal cord)

Botulinum exotoxin

Produced by Clostridium botulinum bacteria, in spoiled food / carcasses

Interferes with PNS, ANS* function (blocks acetylcholine release)


Insecticides, parasiticides

Excitatory, ANS and CNS; neuropathy, myopathy (less frequently seen)



Mixed (excitatory +/- depressant)

Ethylene glycol


CNS depressant


Parasiticide (heartworm preventative)

CNS depressant

*CNS = central nervous system; PNS = peripheral nervous system; ANS = autonomic nervous system

Clinical Presentations

Historical factors most consistent with intoxication include: acute / peracute onset of clinical signs, particularly if these are seen in more than one co-inhabiting animal; compatibility of clinical signs; and/or a history of exposure or access to toxin(s). If the extent of exposure to a toxin is known, the likelihood of such a dose to cause clinical signs can be determined by comparing the mg of toxin ingested to the animal's body weight (mg/kg dose), and comparing this to published toxicity values (if available). For example, if a small animal has ingested less than 20 mg/kg of chocolate the development of clinical neurotoxic signs can be considered unlikely. Due to the non-pathognomonic nature of the signs seen with many of these agents, in cases where exposure has not been witnessed a diagnosis of the specific toxin responsible for the animal's clinical signs can be difficult. However, antemortem diagnostic tests are available for certain common neurotoxins, including ethylene glycol, metaldehyde, lead, recreational drugs, organophosphates/carbamates, strychnine, and tremorgenic mycotoxins.

Neurologic signs seen in small animals exposed to excitatory neurotoxins (i.e., methylxanthines, pyrethroids, amphetamines) commonly include hyperactivity, generalized seizures, tremors, ataxia, and/or opisthotonus. Conversely, common presentations of animals exposed to inhibitory neurotoxins, such as ivermectin, include disorientation, depressed mentation, and/or ataxia. Mixed nervous system effects may also be seen, depending on the degree of exposure. For example, while high doses of bromethalin may induce CNS excitation, more limited exposure will frequently induce CNS depression in small animals. Toxins (e.g., organophosphates, carbamates) may also influence autonomic nervous system function, leading to characteristic clinical findings such as salivation, lacrimation, urination, and defecation ("SLUD"). In these patients diffuse neurologic involvement may also be seen, in the form of skeletal muscle tremors, seizures, and/or hyper-excitability due to effects of the toxin on the central and peripheral nervous systems. Lastly, animals exposed to neurotoxins frequently manifest multi-systemic involvement, including cardiac, gastrointestinal, respiratory, ocular, and/or acid-base status anomalies.

Treatment Overview

The overall goals of therapy include: stabilization, reduced toxin absorption (decontamination), enhanced toxin excretion, specific antagonism of the agent's effects (if applicable), along with monitoring and supportive care. Upon presentation, assessment and stabilization of vital parameters is essential. Abnormalities such as hyperthermia, cardiac arrhythmias, and respiratory distress are commonly seen in these patients, and must be identified and addressed early on, along with assessments of glycemic status, electrolyte levels, and acid-base status. If seizure activity is present, diazepam is routinely administered, although alternative drugs such as phenobarbital or pentobarbital may be used if diazepam does not stop the seizures. Treatment with longer-acting anti-epileptics such as phenobarbital during recovery is often necessary as well. Muscle relaxants such as methocarbamol may be used to reduce tremors and/or muscle spasms.

Recommended first line treatment options once the animal has been stabilized include the following:

Administration of an emetic agent such as 3% hydrogen peroxide or syrup of ipecac may be performed by the animal's owner prior to presentation, within 2 hours of toxin exposure, particularly if delayed transit to a medical facility is anticipated. At presentation emesis may also be induced using apomorphine (dogs) or xylazine (cats). Intravenous, intramuscular, or placement of the drug in the conjunctival sac are preferable modes of administration for apomorphine, as oral absorption can be less effective. Induction of emesis is contraindicated in animals that are unable to guard their airway (i.e., sedated/comatose, abnormal pharyngeal reflexes, seizures), if caustic or volatile agents have been ingested, or in hypoxic or dyspneic patients, as the risk of complications such as aspiration of stomach contents would be highest in these patients. In these cases, gastric lavage through a stomach tube under sedation or anesthesia (with a guarded airway) may be used for decontamination.

Decontamination may not be necessary in patients where the degree of exposure is well below reported toxic doses or in cases where emesis has been induced prior to presentation. If dermal toxin exposure is suspected bathing may be a necessary means of decontamination, taking care to avoid aspiration of bath water and/or hypothermia.

Since vomiting removes a limited quantity (40-60%) of total stomach contents, additional decontamination efforts must be undertaken. Oral administration of an activated charcoal suspension within 2 hours of exposure in animals that are able to swallow, followed by osmotic or saline cathartics such as sorbitol, magnesium sulfate (Epsom salts), magnesium hydroxide (Milk of Magnesia) is recommended. Activated charcoal non-covalently binds to most toxic agents within the gastrointestinal tract, allowing their safe and more rapid excretion. Multiple activated charcoal doses (without cathartics) may be used in patients exposed to toxins with enterohepatic circulation or prolonged release formulations of a toxin. However, in these instances only activated charcoal solutions that do not contain cathartics should be used. In patients that are unable to swallow effectively activated charcoal and cathartics may be administered through the gastric tube following gastric lavage.

Specific toxin antidotes (see table below) may be used to neutralize (chelate) toxins, antagonize their pharmacologic effects, or reduce the breakdown of toxins with active metabolites. Additionally, careful monitoring and supportive care are essential components in the management of intoxicated patients. Airway management, oxygen therapy, temperature monitoring, environmental modification (e.g., minimal environmental stimuli in cases of strychnine intoxication), and treatment of seizures and/or tremors can significantly impact the patient's outcome. Diuresis with intravenous fluids may aid in the correction of electrolyte and/or acid-base alterations, and can be used to enhance the elimination of renally excreted toxins. Caution should be exercised in patients with previously existing organ dysfunction. Lastly, modification of the patient's urinary pH (ion-trapping) may enhance the elimination of certain toxins, such as ethylene glycol and strychnine. This is contraindicated, however, in patients with pre-existing acid-base alterations.

Table 2. Small animal antidotes for common neurotoxic agents.



Mechanism of action

Ethylene glycol (EG)--Dogs

Fomepizole (4-aminopyridine)

Inhibits EG metabolism by alcohol dehydrogenase

Ethylene glycol--Cats


Competes with EG for hepatic metabolism


Calcium disodium EDTA

Lead chelating agent; acute treatment


Lead chelating agent; chronic treatment

Succimer (cats)

Lead chelating agent; chronic treatment

Organophosphates (OP), carbamates


Block acetylcholine (muscarinic only)

Pralidoxime chloride (2-PAM)

(OP toxicity only)

Reactivates acetylesterase, binds OP


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Speaker Information
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Sofia Cerda-Gonzalez, DVM, DACVIM (Neurology)
Cornell University - College of Veterinary Medicine
Ithaca, NY

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