Common neurological diseases in food animal (Proceedings)
Maybe this doesn't really fit "common" but it is always interesting to hear about cases. The main thing about rabies in cattle (and other species) is that signs are quite variable and inconsistent. Certain signs should be "red flags" for bovine rabies. Oftentimes cattle with rabies will have some history of hindlimb ataxia, weakness, or paralysis (this in itself is typical of many bovine diseases but for cattle exhibiting these signs, rabies should be considered).
Maybe this doesn't really fit "common" but it is always interesting to hear about cases. The main thing about rabies in cattle (and other species) is that signs are quite variable and inconsistent. Certain signs should be "red flags" for bovine rabies. Oftentimes cattle with rabies will have some history of hindlimb ataxia, weakness, or paralysis (this in itself is typical of many bovine diseases but for cattle exhibiting these signs, rabies should be considered). Constant straining with or without rectal prolapse is a red flag. Don't expect to find bite wounds because of the length of the incubation period. Three forms are described and include 1) cerebral or furious: aggressive behavior, photophobia, hyperesthesia, straining, and convulsions), 2) brainstem or dumb form: depression and dementia with ataxia, excessive drooling and pharyngeal paralysis and 3) spinal cord or paralytic form: progressive ascending paralysis. Common cattle signs in order of most common are salivation, bellowing, aggressiveness, paresis or paralysis and straining. A 5-year-old cow died of rabies 4 days after being presented with persistent unrelenting rectal straining. The rectal straining was controlled with caudal epidurals. Occasional yawning and bilateral rear limb knuckling developed and got progressively worse. This cow did not appear to have a serious change in mentation (not aggressive nor more docile) and was not ever seen attempting to eat or drink.
Diagnosis is via brain FA. Histopathology may show eosinophilic intracytoplasmic Negri bodies in neurons. If only spinal cord disease is present, virus and Negri bodies may not be found in the brain (only the spinal cord). Thus, premature euthanasia may not be prudent. The incubation period varies from 2 weeks to 6 months depending on site of inoculation. A bite on the rear foot may take 6 months before clinical signs appear whereas a bite on the nose may only take a couple of weeks. Once clinical signs appear, most animals die by 10 days. I have heard of a couple of cases surviving > 15 days. The rabies virus passes along neurons within the nervous system to the brain. Initially, there may be hyperactivity of affected neurons with signs such as hyperesthesia, tremor, straining, and salivation. Eventually the neurons die; resulting in flaccid paralysis, dysphagia, and anesthesia. Treatment is not a practical option. Vaccines are available but not routinely used in cattle due to expense and relatively low incidence.
Listeriosis is defined as an acute bacterial meningoencephalitis of ruminants characterized by circling and cranial nerve deficits. The clinical signs typically relate to caudal cranial nerves (V thru XII)....thus affected cattle can usually see. General signs of fever (last 2-4 days), anorexia, depression, excessive salivation may be seen as well. Neurological signs include proprioceptive deficits, head-pressing, depressed consciousness (due to lesions of the reticular activating system), constant or sporadic walking or circling (the latter due to lesions of the basal ganglia). Sometimes the affected animal, because of the desire to circle, gets stuck against a wall or gets stuck in the corner. Spinal reflexes may show mild to moderate hypertonia and hyperreflexia in the limbs contralateral to the lesion. Lesions of the cerebellar peduncles may result in a head tilt opposite of the direction of circling. The primary cranial deficits (many or none may be present) include: dropped jaw and or facial anesthesia (CN V), medial strabismus on the ipsilateral side of the lesion (CN VI), ptosis, loss of menace, absent palpebral reflex, drooped ear, loss of levator nasolabialis muscle function (one open, one semi-closed nostril), decreased lip tone (CN VII), nystagmus (any type and inconsistent) that changes as the position of the head is altered and head tilt to the ipsilateral side of the lesion, a tendency to circle to the side with the lesion (CN VIII), stertorous breathing, dysphagia and paresis or paralysis of the tongue (cranial nerves IX, X, and XII). With unilateral lesions, the tongue may protrude from the side of the mouth ipsilateral to the lesion. If not treated in time, signs will progress to convulsions, coma and death. Diagnosis is presumptive and based on clinical signs and response to therapy. There is usually NOT an inflammatory leukogram. A CSF tap can be helpful. The CSF tends to be a mononuclear pleocytosis (> 12 cells/ul) with a mildly elevated protein (> 40 mg/dl). The organism can be cultured from CSF or microabscesses but requires refrigeration, enrichment and a long incubation time.
Treatment can be successful but may take from 1 week to 1 month. Fluids are necessary for those that cannot swallow or have difficulty swallowing. Fluids should be alkalizing because of salivary bicarbonate loss (due to persistent drooling in those that can't swallow). Several different antibiotics are effective with the standard oxytetracycline @ 10 mg/kg BID IM, IV, or SQ or procaine penicillin G @ 40,000 IU/kg IM 3-4 x day for 1 week followed by half this dose SID for another 1-2 weeks being the drugs of choice. Under hospital conditions, we will use potassium penicillin @ 44,000 IU/kg IV 3-4 x day for 3-5 days and then follow with one of the antibiotics above on valuable and pet animals. The disease agent is the gram-positive bacterium Listeria monocytogenes. This is probably one of the two most common neurologic diseases of ruminants. Cases are mostly sporadic but occasional outbreaks occur (outbreaks usually point to a common feedstuff). CNS infection may occur hematogenously or by ascension of a cranial nerve (some evidence points toward CN V). Silage is the most commonly implicated source but cases certainly occur without the presence of silage. Properly ensiled silage is not supportive of Listeria growth (proper silage should be anaerobic and have a pH < 5.4). Listeria may be shed in the feces of carriers and may be found in rotting vegetation. It may survive in soil up to 2 yrs and is very resistant to environmental factors. Commercial vaccines are not available. The mortality rate for untreated cases is nearly 100%. Most livestock treated properly and in a timely manner survive though some may have permanent neurologic deficits.
Polio is defined as a neurologic disease of young (usually) ruminants characterized by blindness due in part to thiamine deficiency. Clinical signs consist of an acute onset of ataxia, tremor, blindness, opisthotonos, convulsions, and recumbency. The rumen is usually unaffected. Unless there has been seizure activity, there is usually no fever. Cranial nerve function is usually normal is except for central blindness and dorsomedial strabismus. Some animals may have a staggering gait and others may wander. Opisthotonus and bruxism are also common findings. Affected livestock often have an absent menace reflex but the blink and pupillary light reflexes are intact. Muscle tremors, seizures, and eventual coma may also occur. Head pressing is relatively common; likely due to cerebral edema.
The diagnosis is often based on clinical signs, history, and response to thiamine therapy. CSF may reveal a slight mononuclear pleocytosis (5-50 cells/ul) and a mild protein elevation (50-150 mg/dl); thus indistinguishable from Listeriosis. Other less common means of diagnosis include red blood cell (RBC) transketolase activity (should be low), tissue thiamine concentrations (may be normal) and postmortem thiamine concentrations of heart, brain or liver (although many labs don't have the capability to run thiamine levels). Necropsy may reveal a swollen, slightly yellow cerebrum. Autofluorescence of a freshly cut surface of cerebral cortex placed under ultraviolet light is good presumptive evidence. Although, autofluorescence may be absent in acute cases that undergo sudden death.
The mainstay of treatment is thiamine (B1) @ 10-20 mg/kg IM or SQ BID to TID for 5 days (can be given IV but can result in death if given too fast; thus dilute with normal saline). Response to appropriate treatment should be evident within 1-2 days. Control convulsions (diazepam or phenobarbital) and provide tender, loving care. Although there can be distinct differences between polio and listeriosis, we almost always treat for both. Polio is most common in young cattle (6-12 months) but seems to affect every age of small ruminants. Outbreaks may occur in feedlots but sporadic cases may occur anytime or place and often without a clear reason. Several rumen organisms can produce thiaminase. A high carbohydrate diet promotes proliferation of the thiaminase bacteria. Thus, polio may be seen secondary to ruminal acidosis.
A 2009 polio mini-outbreak occurred on a purebred Angus ranch and was thought due to access to creep feed. The initial presentation was acute convulsions, inability to stand, and apparent blindness in a 6 month old heifer. Thiamine, flunixin meglumine, and dexamethasone were administered just prior to loading the heifer on the trailer to bring to the veterinary school. By the time the heifer arrived, she no longer was convulsing and had apparently stood. A physical exam revealed absence of menace but normal papillary light reflexes, dorsomedial strabismus and bruxism. The heifer seemingly responded to thiamine therapy and was standing but ataxic and obviously blind the evening of the first day. By the next morning, the heifer was able to rise on her own, ambulate, eat and drink. An evaluation of the rumen content revealed a normal pH but few live protozoa and no live large protozoa. A rumen transfaunation was performed as ruminants rely on ruminal microbial thiamine. The heifer was discharged ~ 1 week after admittance but was still blind. Although it took ~3 months, the heifer has apparently regained her vision. Three other calves were subsequently affected in this herd. The owner decreased the grain feeding, increased roughage and added thiamine to the ration. In problem herds, the diet may be supplemented with thiamine HCl or mononitrate at 10-30 mg/kg of feed or 300 mg/head daily.
Feedlot diets high in sulfates have been implicated; feed additives such as gypsum, ammonium sulfate, corn processing co-products, cruciferous crops, molasses, and fertilizers and sulfates in water may also contribute. Competitive thiamine analogues such as amprolium may predispose. A 2 year old Holstein cow was erroneously given 5 times the label dose of amprolium for coccidia. The cow was found convulsing 2 hours later. She was treated with thiamine and made a complete recovery shortly thereafter. The prognosis is excellent when therapy is given early in the disease. If the animal is still ambulatory, the prognosis is good but permanent blindness may result.
The pathophysiology essentially results in a swollen cerebrum. Thiamine is a cofactor for transketolase. Transketolase is the rate limiting enzyme for cerebral glycolysis. Glycolysis produces ATP. ATP is necessary for the Na-K pump. Thus when thiamine is deficient, water follows Na into the cerebrum and results in cerebral edema and subsequent necrosis of the gray matter.
Tetanus is a neurologic disease characterized as a progressive muscular rigidity due to a Clostridium tetani neurotoxin. The clinical signs include initial stiffness in movement, which progresses over a 24 hr period to spasticity, mouth foaming due to inability to swallow, "airplane ears", sawhorse stance, hypertonia, lips may be retracted toward the poll, trismus ("lockjaw"), ventrolateral strabismus and dilated pupils in advanced cases. Eventual lateral recumbency and muscular rigidity that becomes worse with auditory, ocular, or tactile stimuli, progressing to respiratory paralysis and death. There is no easy means of definitive diagnosis (there are no reliable clinical or pathological tests or findings) which is predominately based on clinical signs. If a wound is obvious, culture of that site may revealed the anaerobic organism. Neurologic examinations should reveal limbs and head are very resistant to passive flexion, a menace response that results in rapid flashing of 3rd eyelid and retraction of the eye.
Treatment can be successful but is also relatively expensive as time must occur for new nerve receptors to develop because once the tetanus toxin is bound, it is not affected by treatment. Treatment involves neutralization of the toxin via antitoxin: suggested dosages range from 1000 to 5000 IU/500 kg; 1000 to 5000 IU/kg;1500 U-100,000 U per animal for 3-5 days. Debridement of the affected area allows oxygen to the area and along with penicillin infusions around the wound may decrease bacterial growth and subsequent toxin production. Parenteral administration of potassium penicillin (22,000 IU/kg 3-4 times a day) or procaine penicillin G (22,000 IU/kg BID) are the drugs of choice. The IV route (K-Pen only) is preferred for valuable or sentimental livestock but is considerably more expensive. Tetanus toxoid is also recommended because the amount of toxin necessary to produce clinical signs does not necessarily produce an immunologic response. Tetanus toxoid should be given at first treatment (at a site distant to the tetanus antitoxin) and a second dose given 1-2 months later. Other treatments are primarily supportive care. Muscle relaxants may be used. The animal should be placed in a dark quiet room (*packing the ears with cotton help to decrease auditory stimuli) and acetylpromazine @ 0.05- 0.1 mg/kg every 4-6 hr as needed or diazepam (0.01-0.4 mg/kg IV as needed). Provide good footing, provide fluids and nutrition, especially if swallowing is dysfunctional. Ruminants may bloat, therefore a rumenostomy may be performed which alleviates the bloat and allows easy feeding and watering. A 10 day old lamb was treated for tetanus and it required 10 days of therapy before it could stand and ambulate on its own. The treatment was many times more expensive than the worth of the lamb. Mortality may reach 80% but cattle surviving for 1 week have a fair to good chance for complete recovery. Improvement may not occur until 2 weeks with clinical signs persistently up to 1 month. There may be some permanent effects. With proper and timely treatment, cattle may be saved but the treatment can be quite expensive (especially for large stock) and this is why commercial cattle are often euthanized.
The organism may be isolated from the soil and from feces of most herbivores. Cases are usually sporadic but epidemics have been reported usually following castration or tail docking procedures (especially when elastrator bands are used). In most cases, the incubation period is 2-4 wks. In dairy cattle, entry via the uterus is thought most common. Spores inoculated into an anaerobic site germinate into the vegetative form. Spores inoculated into aerobic sites are highly resistant to host defenses and may remain in situ for years. Cattle are susceptible but have not typically been vaccinated for tetanus but vaccines are available and should be used in problem herds. Some dairy herds that dock tails will routinely use the vaccine as tail docking has been implicated in tetanus cases. Tetanus is one of the standard vaccines used in small ruminants. Vaccination may not provide 100% protection but is pretty good. Horses have developed tetanus despite being previously vaccinated.
Lead poisoning presents as a diffuse cerebral disease. Cases may present with bloat, tenesmus with diarrhea or constipation, hyperesthesia, muscle twitching, rapid spastic twitching of the eyelids, ataxia and weakness. Signs progress to aggression, convulsions, central blindness, wandering, head pressing, opisthotonos, bruxism, bellowing, and eventual death. Blood work is often helpful. Basophilic stippling and nucleated RBCs may occur without signs of RBC regeneration (seldom anemia). Ante mortem diagnosis is based on clinical signs, history (access to lead batteries, grease, oil etc), and lead levels of whole blood (EDTA or heparin) or liver biopsy. Blood lead levels may or may not be elevated (>0.6 ppm is definitive). Urinary lead excretion following EDTA treatment is also confirmatory. Evaluation of the feed lead levels should be considered as one case report describe a lead battery accidentally being mixed with the feed and being fed to feedlot calves (Jones et al., 2007). Postmortem diagnosis is based on lead levels of liver, kidney, and stomach contents.
Treatment can be successful but known cases are often euthanized. If signs are mild, slow resolution can occur without treatment. Treatment consists of removing access to the lead. Thiamine should be administered @ 1g per 300 kg. Magnesium sulfate laxatives help form insoluble lead sulfides. Calcium EDTA chelation therapy over several days is the treatment of choice (50-100 mg/kg slowly IV SID or BID for 2-5 days is one regimen). The effectiveness of this treatment can be evaluated by evaluation of urine lead levels (should be elevated).
The single lethal dose in cattle ranges from 220-400 mg/kg for adults and 600-800 mg/kg for calves. Sources include lead paint, linoleum, caulking compounds, batteries (auto), old machinery oil or grease, high concentrations of lead may accumulate in forage along busy roads and heavy industrial pollution of forages. If lead is suspected, an inspection of the area of the affected cattle should be carried out even if the owner claims there are no sources of lead or that the cattle have been on the area for years. Lead interferes with normal heme synthesis, which results in decreased oxygen-carrying capacity of RBCs. Signs are caused by an ischemic effect on cerebral cells. Cerebral edema may result. The primary effect is on neurons but the vascular endothelium and peripheral nerves may also be affected. The prognosis is fair providing treatment is aggressive and initiated early.
Jones CW, Checkley SL, Booker CW, et al. Investigation of accidental lead exposure in feeder cattle. Proceedings Annual Convention American Association Bovine Practitioners 2007, 40:77-78.