Weakness and/or Depressed Mentation

In a CSF pharmacokinetic study of florfenicol in calves, the maximum concentration of florfenicol attained in CSF was 4.67 ± 1.51 pg/mk following a single intravenous dose of 20 mg/kg.²⁶ The levels remained above the minimum inhibitory concentration (MIC) for Histopbilussomni over a 20-hour period. This concentration is below the MIC₉₀ for E. coli. Bactericidal antibiotics are proposed to be more effective for treatment of meningitis in humans, and it is recommended that the con­centration of antibiotic in the CSF should be maintained at 10 times the MIC of the target pathogen.³⁰ Unfortunately, owing to the lack of CSF pharmacokinetic data in cattle, antimicrobial treatment of meningitis is an inexact science. Antiinflammatory therapy and nursing care should be instituted as described previously for neonatal septicemia. Convulsions in calves can be treated with diazepam (0.1 to 0.2 mg/kg IV). This can be repeated every 30 minutes until convulsions are controlled.

Metabolic Acidosis

Profound weakness associated with metabolic acidosis or “strong ion” acidosis is commonly observed in calves with diarrhea and sporadically in kids (“floppy kid syndrome”) and calves without other clinical signs of disease.^32,33 This acidosis is often associated with an increased concentration of D-lactate (the anion of D-lactic acid) resulting from bacterial fermentation of carbohydrates in the GI tract of milk-fed calves. Clinical signs of impaired CNS function, including ataxia and coma, in sick calves have been attributed at least partially to the increased D-lactate concentrations.^34,35Assessment of weak neonatal ruminants for the presence of metabolic acidosis is a critical part of the physical examination. Correction of the acidosis by intravenous administration of bicarbonate produces a rapid recovery. An improvement in mentation and strength should be observed within 12 hours; persistent depression is likely to reflect incomplete correction of acidosis, sepsis, hypoglycemia, hypernatremia, or hyponatremia.

Hypoglycemia

Hypoglycemia is a common sequela to withdrawal of milk for more than 48 hours, especially in cold weather. Affected calves are weak or recumbent but appear to be normally hydrated or minimally dehydrated.³⁶ They are often emaciated and can occasionally have neurologic signs, including facial twitches, convulsions, opisthotonos, and coma. They will respond to a bolus of 50% dextrose or an infusion of 5% glucose, but often this response is temporary, especially in calves with severe malabsorptive disease. It is important to rapidly restore adequate energy intake to ensure resolution of these cases. Starvation and hypothermia resulting from mismothering are common causes of weakness in neonatal lambs. Similarly, weakness, poor body condition, and increased susceptibility to infectious diseases are observed with protein-calorie malnutrition induced by feeding poor-quality or incorrectly mixed milk replacers.³⁷ Hypoglycemia is also frequently seen in calves with neonatal septicemia, as discussed previously. In a recent study that reported serum glucose concentrations in more than 10,000 calves 3 weeks of age and younger, the presence of severe hypoglycemia (glucose ≤36 mg/dL or 2 mmol/L) was associated with a poor survival rate, as only 20.6% of these calves survived compared to 74.0% of calves with normal glucose levels.³⁸

Hyponatremia

Hyponatremia occurs when loss of isotonic fluid through the GI tract is replaced by free water or hypotonic solutions. The latter often occurs when too much water is added when making up an oral electrolyte solution. Hyponatremia may also occur when isotonic oral electrolyte solutions are administered to calves with compromised sodium absorption capacity. This may be a result of severe pathologic changes or an inadequate level of agents that facilitate sodium cotransport within the oral electrolyte solution. Hyponatremia results in a fluid shift from the extracellular space to the intracellular compartment along the osmotic gradient, and the resultant swelling of the cells can result in neurologic disturbances, depression, disori­entation, and even convulsions.³⁹ Hyponatremia should be considered in calves with serum sodium less than 132 mmol/L; calves with serum sodium less than 120 mmol/L have severe hyponatremia.

The goal of therapy is to restore serum sodium levels to greater than 125 mmol/L over the first 6 hours and then to restore to normal levels over 24 hours.³⁹ In hypovolemic calves the initial treatment should be achieved using normal saline, and in normovolemic calves hypertonic saline should be used for the initial treatment, since the administration of large fluid volumes will exacerbate cerebral edema. If the calves are also suspected to be acidotic, this should be corrected with sodium bicarbonate solutions of appropriate tonicity.

The amount of sodium required in the first 6 hours to raise the sodium level to 125 mmol/L can be calculated as follows.³⁹

mEq Sodium = (125 - Measured mEq serum sodium)

? (0.6 ? Body weight in kg)

Calves should then be maintained on a sodium-containing isotonic fluid, such as normal saline or lactated Ringer, and treated with oral electrolyte solution as appropriate. The sodium level should be monitored frequently in the first 24 hours because of unknown losses through the GI tract as well as unknown kidney function in a severely dehydrated patient.

Hypernatremia

Hypernatremia (also known as sodium or salt toxicity) is a relatively common problem encountered in young calves. These cases are generally a result of the calf ingesting excessive concentrations of salt without an adequate balance of water to balance the sodium load. The most common clinical scenarios involve calves ingesting milk replacers high in sodium without access to fresh water^40,41 or calves that are being treated for diarrhea and receive oral electrolyte solutions with high sodium concentrations.^42,43 Recently, cases of hypernatremia in calves have been observed associated with the use of high-sodium water on farms. Affected calves are typically younger than 3 weeks of age and often (but not always) exhibit neurologic signs.

The volume of the extracellular fluid (ECF) is determined by the total body sodium content, whereas the osmolality and sodium concentration of the ECF are determined by sodium and water balance. Multiple control mechanisms work in the body to detect and respond to changes in the osmolality and volume of the ECF. These homeostatic mechanisms primarily control retention and excretion of sodium. Examples of regula­tory control include the thirst response (water ingestion) and excretion or retention of sodium by the kidneys. Although it sounds simple, these are under complex control by multiple hormonal pathways, including antidiuretic hormone (ADH), atrial natriuretic peptide (ANP), the renin-angiotensin- aldosterone system (RAAS), and the autonomic nervous system. A complete discussion of the physiology of sodium and water homeostasis is beyond the scope of this chapter, but readers are referred to other recent review articles for more detailed information.^44,45 When calves take in too much sodium, this results in expansion of the ECF at the expense of intracellular fluid (ICF) in order to return the osmolality of the blood to normal (relative dehydration). In cases where there is no water intake, fluid loss is associated with reduction in total body water content (absolute dehydration). In cases of hypernatremia, the brain has to adapt to the hyperosmolar state, which typically involves shrinkage of neurons as water follows concentration gradients and moves into the hyperosmolar CSF and plasma. This results in dehydration of neurons and brain shrinkage. As the brain moves away from the calvaria, disruption of the normal blood supply can occur.⁴⁴ Neurologic signs often worsen during treatment of calves with hypernatremia, since rapidly lowering the sodium concentration with free water will allow water to flow into neurons, causing the already shrunken cells to swell, resulting in cerebral edema. This edema can lead to seizures and in many cases death.²⁸ Hypernatremia is defined as a serum or plasma sodium concentration of 160 mEq/L or greater, and neurologic signs of salt toxicity can be seen. Serum sodium concentrations greater than 180 mEq/L generally indicate a guarded to poor prognosis. Sodium concentrations in the CSF of cattle normally range from 130 to 142 mEq/L but are typically above 160 mEq/L in animals with hypernatremia.⁴⁶ Ocular fluid represents a good sample to submit to the diagnostic laboratory in dead calves, since it does not change appreciably with advancing postmortem autolysis and provides a stable representation of sodium levels at the time of death. Ocular fluid sodium concentration is reported to be about 95% of the serum sodium value, and levels are significantly elevated in cattle with hypernatremia.⁴⁶ In cattle that are dead, the entire brain or cerebral cortex should be submitted to a diagnostic laboratory for sodium analysis and histopathology. Typically no gross lesions of the brain are apparent at necropsy in cases of hypernatremia, and histopathology is nonspecific with cerebral edema present. Therefore submitting fresh brain and/or ocular fluid for sodium analysis in addition to requesting histopathology is critical. Sodium concentrations in brain tissue are generally greater than 2000 μgλg (ppm) in calves with hypernatremia.

Early clinical signs of hypernatremia include lethargy and depression, which, without blood work, cannot be differentiated from many other possible diseases such as acidemia, dehydration, hypoglycemia, or hypothermia. More advanced clinical signs of hypernatremia include twitching of facial muscles, muscle rigidity, tremors, and myoclonus.^28,44,47 Calves will demonstrate seizure and/or coma activity near death. Prognosis in these calves is often guarded to poor even with aggressive treatment.

Treatment of calves with chronic hypernatremia is often very difficult and should be reserved primarily for valuable animals. Classic recommendations call for sodium concentra­tions to be lowered very slowly, since replacing free water too rapidly could cause neurons to swell, cerebral edema, and a worsening of neurologic signs. The total body free water deficit can be calculated using the following formula:

0.6 ? Body weight (kg) ? ([Current serum sodium

concentrations/Normal serum sodium concentration] -1) However, if this fluid is given rapidly, neurologic complications will often arise. In general the recommendation is to formulate fluids that have a sodium concentration approximately equal to that of the calf.^28,44,47 This can be done by adding small volumes of hypertonic saline (1.2 mEq/mL) or 23.4% sodium chloride (4 mEq/mL) to whatever fluid type you have chosen to give the calf. For example, if the calf has an acidemia, additional sodium can be added to isotonic sodium bicarbonate (sodium concentration of 156 mEq/L). However, if the calf has a relatively normal pH, additional sodium could be added to 0.9% saline (sodium concentration of 154 mEq/L). The idea is to decrease the sodium level of the calf very slowly over several days to avoid cerebral edema. A case example below will illustrate the calculation.

A 45-kg Hereford calf had clinical signs of hypernatremia. The calf had a serum sodium concentration of 187 mEq/L. To calculate the free water deficit in this calf we would multiple 0.6 ? 45 ? ([187 - 145) - 1)] to get a free water deficit of 7.82 L. In this example we used 145 to represent the “normal” serum sodium concentration for a calf. If we wanted to give 0.9% saline to this calf (154 mEq of sodium per liter), we would need to add 33 mEq of additional sodium to reach the calf's level of 187. The simplest way to do this would be to add a small volume of hypertonic saline (33 mEq/1.2 mEq/ mL = 27 mL of hypertonic saline added per liter of fluids). You could also add hypertonic saline to isotonic sodium bicarbonate if the calf had an acidemia. Since isotonic sodium bicarbonate has a sodium concentration of 156 mEq/L, you would need to add 31 mEq of sodium. Be careful about adding large volumes of dextrose to these solutions, as that will lower the sodium concentration.

Although not always successful, a report of treating several hypernatremic calves with 5% dextrose either alone or in combination with sodium bicarbonate has been published.⁴² In this study calves were given 2 to 4 L of 5% dextrose at a slow drip (about 500 mL/h) and had their serum sodium concentrations decreased much faster than is usually recom­mended. However, the four calves in the case report were treated successfully. Although this approach may not always work and could easily result in cerebral edema, it may be practical for times when the clinician does not have the ability to formulate fluids or monitor serum sodium concentrations frequently. In calves with chronic hypernatremia where “idiogenic osmoles” have formed, it is likely critical to lower sodium levels slowly, whereas the clinician may be able to lower sodium more rapidly in cases of acute hypernatremia.

If the calf's neurologic signs get significantly worse after fluid therapy has started, cerebral edema should be suspected. Treating cerebral edema is difficult but imperative to prevent further brain damage and/or death. Corticosteroids are the easiest choice normally; however, they are only marginally effective in treating moderate to severe cases of cerebral edema. Mannitol (25%) at 1 g/kg given IV over 30 minutes or an oral solution of glycerin diluted 1 : 1 with water has also been recom­mended for severe cases of cerebral edema but can be more difficult to obtain.²⁸

Hypernatremia is largely avoidable by proper management. Since hypernatremia occurs largely under one of two condi- tions—(1) calf ingests too much sodium without an adequate volume of water in a short period of time, or (2) sustained water deprivation—the key becomes preventing both of these conditions from occurring. Whole milk is typically fairly low in sodium concentration, so typically calves fed whole milk have little problem with sodium toxicity unless given a large amount of oral electrolytes. Some milk replacer products can have significantly higher sodium concentrations as compared to whole milk (up to 85 to 100 mmol/L). Water quality is another factor that can have a profound effect on the amount of sodium calves ingest. Water that has been through a softening process to remove minerals such as calcium and magnesium can often have very high sodium concentrations and therefore should not be used to dilute commercial milk replacers unless a water analysis has been performed and sodium levels are less than 100 ppm. In one case report of salt poisoning in calves, milk replacer samples diluted with farm water had sodium concentrations ranging from 171 to 185 mmol/L.⁴⁰ When cases of hypernatremia are diagnosed on a farm, veterinarians should not forget to consider the drinking water source as a possible source of excess sodium.

In addition to watching how much sodium we feed calves in their normal milk diet, attention must also be given to the feeding of oral electrolyte solutions in calves with diarrhea. When homemade oral electrolyte products are used or when labeled mixing directions are not followed correctly, sometimes the sodium concentration fed to calves can be extremely high. In some cases oral electrolyte products are purchased in bulk containers, and more powder is added to 2 L of water than indicated in the directions. Multiple case reports describing hypernatremia in calves have involved the feeding of unknown amounts of oral electrolyte solution to calves multiple times per day.^42,43 This situation is exacerbated when calves do not have access to fresh water or when the fresh water also contains high sodium concentra­tions. In one case report, hypernatremia was diagnosed associated with neurologic signs and deaths in a group of 6- to 10-month-old Holstein calves that had access to a salt block without free-choice water available.⁴⁸ So ultimately, paying attention to the calf feeding program and the diarrhea treatment (oral electrolyte) feeding protocol for the farm is critical, along with ensuring that calves always have a supply of fresh, good-quality water.

Neuromuscular and Musculoskeletal Disease

Primary neuromuscular or musculoskeletal disease should be considered when weakness is not associated with depressed mentation. Weakness associated with micronutrient deficiencies results from myodegeneration (white muscle disease, selenium, and vitamin E) or demyelination (copper, enzootic ataxia). If weakness is detected in one or more limbs immediately after birth, peripheral nerve and muscle damage associated with birth trauma should be ruled out (see Box 20.1). Femoral nerve paralysis may be observed in calves following a “hip lock” dystocia.⁴⁹ A condition resembling congenital myasthenia gravis has also been described in Brahman calves.⁵⁰

Nutritional myodegeneration associated with selenium or vitamin E deficiencies may produce localized (dysphagia) or generalized paresis. Neonatal small ruminants appear to be particularly susceptible. Affected lambs may be unable to rise; others can stand but may be unable to nurse because they are unable to raise their heads. Diagnosis is based on clinical signs, increased serum creatine kinase concentration, and reduced whole blood glutathione peroxidase and/or selenium concentrations (see Chapter 42). Vitamin E deficiency is observed when pregnant ewes are fed stored forage low in vitamin E; the clinical signs in affected lambs are identical to selenium deficiency, but selenium status is adequate. Since vitamin E is labile, serum should be harvested quickly after blood collection, frozen, wrapped in aluminum foil, and sent via express mail on ice.

Paraplegia and tetraplegia are commonly associated with spinal cord compression. Compression of the spinal cord in neonates most commonly results from vertebral body mal­formations, osteomyelitis, or fractures. Generally vertebral body malformations occur sporadically; genetic, nutritional, and environmental factors have been implicated.^51,52 In older calves, underlying metabolic bone disease (copper, vitamin D, or phosphorous deficiency) may increase the propensity for fractures to occur. Osteomyelitis and vertebral body abscess may be sequelae to bacteremia following neonatal septicemia or pneumonia.⁵³ The frequent isolation of Trueperella pyogenes from vertebral body abscesses in ruminants suggests that chronic respiratory infection is more frequently the source in these species.^54,55 Vertebral body abscesses in lambs are occasion­ally a sequela to infected docking wounds. Leukocytosis and hyperfibrinogenemia are commonly observed in neonates with vertebral body abscesses. In most instances vertebral abscesses do not infiltrate the pachymeninges, so the CSF either is normal or has a mild elevation of protein and/or a mild pleocytosis.^53,54

Differential diagnoses for paresis in goat kids include caprine arthritis encephalitis virus (CAEV) and enzootic ataxia. Enzootic ataxia is also common in lambs. Progressive ataxia and paresis or paralysis is a feature of both diseases. There are two forms of enzootic ataxia (swayback): the neonatal and the delayed types. In the neonatal condition, animals are affected at birth; in the delayed type, signs of incoordination appear at 14 to 30 days of age.⁵⁶ Most affected kids are afebrile, bright, and alert, and they will continue to eat if it is physically possible. Enzootic ataxia is associated with low liver copper content and occasionally low serum copper concentration. It has been proposed that reduction in the activity of the copper-dependent enzyme cytochrome oxidase impairs phospholipid synthesis and subsequently myelin production. Microcytic anemia and increased fragility of bones may be observed in more chronic cases.⁵⁷ The copper, molybdenum, and sulfur content of the maternal diet should be evaluated and adjustments made for copper deficiency or molybdenum or sulfur excess.

Goat kids with the neurologic form of CAEV will have mild to moderate fevers and evidence of cerebral involvement. Cerebral signs commonly identified include depression, head tilt, torticollis, and circling. Evidence for CAEV includes CSF pleocytosis and increased CSF protein and a positive CAEV (agar gel immunodiffusion, or AGID) or enzyme-linked immunosorbent assay (ELISA) test.⁵⁸ Both the neurologic form of CAEV and enzootic ataxia carry a poor prognosis.

A complete neurologic examination is an important com­ponent of the work-up of the weak neonate. In particular, it should be noted if the weakness is accompanied by signs of depression and diffuse cerebral disease. Strength is preserved if ataxia is caused by cerebellar disease. Limb reflexes should be tested to establish whether components of the spinal reflex pathways are involved in the disease process (sensory nerve, lower motor neuron, neuromuscular junction, muscle). Animals with other types of spinal cord disease (e.g., trauma, vertebral malformations, enzootic ataxia) may also show weakness and ataxia yet appear clinically to have normal cerebral function. Virtually any severe systemic disease such as generalized infec­tion can cause both profound depression and weakness in a neonate without the presence of actual brain pathology. Intermittent signs of severe weakness and depression may be caused by the narcolepsy-cataplexy syndrome.

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