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CNS disease diagnostics

Published: February 17, 2014
By: Darin Madson (Iowa State University)
Introduction
Central nervous system (CNS) disease or like diseases can be frustrating circumstances in growing pigs, even if there are only a few animals affected. The challenges we as swine veterinarians face is accurately diagnosing these issues, mitigating, and then preventing future problems. The intent of presentation/proceedings to provide guidance, understanding, and sample collection tips for CNS disease scenarios or disease presentations that may arise in nursery aged pigs.
Disease diagnosis is different for each of us. It basically comes down to how each of us thinks followed by incorporating previous experiences. What you see, determine, or link together with a thorough investigation in the clinical setting will hone in your diagnostics skills when it comes to particular pathogens or syndromes, but this will also guide proper sample submissions when CNS disease problems are not so clear cut from the normal.
Bear in mind that not every condition with perceived neurological signs is infectious or is even related to the central nervous system. Too often we as veterinarians make broad assumptions on the cause of disease. There is nothing wrong with this. Experience usually lends our differentials to be true. However, not understanding potential differential will hinder finding the actually etiologic cause of the clinical syndrome.
Oh, where to begin? Well, how about on a complete clinical examine of those pigs displaying signs of disease. Neurology was maybe not your favorite during veterinary school, but that does not mean that we should forget about proper procedure. An exam can localize the issue or possibly disprove CNS involvement all together. Some clinical examples would include proprioceptive defects, varied coordinated movement, posture and mentation. A second key aspect of an investigation is gathering a detailed history including recent procedures such as vaccinations, feed changes, or mechanical issue within the facility affecting air, feed or water.
Before we start listing conditions, a mini review of basic neurology may help. The cerebrum is responsible for behavior, voluntary movement and consciousness; it is the hub for normal thought. “Down paddling” and nystagmus is a loss of voluntary movement of the limbs and ocular muscles and therefore would indicate cerebrum involvement. This is most commonly in the form a bacterial meningitis, but viruses and toxins (i.e. salt), can also result in this clinical presentation. Seizures, tremors, and hyperesthesia are other clinical signs that would indicate the cerebrum is involved. If normal or perceived normal mention is apparent, the cerebrum is likely not affected. The cerebellum is responsible for coordinated movement, balance, and posture. Ataxia, proprioceptive deficits, and incoordination are typically present with defects in the cerebellum. However, spinal cord issues can also present with similar clinical problems as seen in with cerebellar disease, and can also include muscle rigidity or flaccidity. Table 1 summarizes clinical signs that can be seen with different segments of the CNS.
I hope that you are not confused yet because we also have to rule out cardiovascular, muscle, bone and joint lesions that may appear as “CNS signs.” This is where your “routine” necropsy is important; don’t just drill down on CNS tissue for sample submission! Pain associated with trauma, broken or weak bones, or inflammation within the axial skeleton can cause incoordination, proprioceptive deficits, or recumbency. However, the pig’s awareness/mentation is typically not altered. Cardiovascular problems resulting in tissue hypoxia may also mimic CNS disease syndromes in certain scenarios.
CNS differentials
Swine medicine is population medicine at its finest. With that said, we are typically dealing with infectious pathogens when CNS disease issues within the nursery phase of production occur. This does not exclude metabolic conditions, toxin issues, or traumatic problems as the cause of clinical CNS disease. Below is a list of common differentials for CNS like diseases in nursery aged pigs. This list is not complete, but captures the vast majority of cases that are typically seen at diagnostic laboratories.
1. Bacterial septicemia: Streptococcus suis, Haemophilus parasuis and Mycoplasma hyorhinis
  • Lesion: Meningitis, but otitis is possible
  • Clinical sign: Nystagmus, “down paddling,” head tilt, and circling
CNS disease diagnostics - Image 1
2. Viral diseases: Porcine Reproductive and respiratory syndrome virus, porcine circovirus type 2, and enteroviruses ( Teschoviruses)
  • Lesion: Encephalitis or meningoencephalitis, typically perivascular. Lesions associated with teschoviruses are in the brainstem
  • Clinical sign: Dulled mentation, seizures, incoordination, ataxia, recumbency and proprioceptive deficits. Knuckling-over and/or posterior paresis more common with Teschovirus infection.
3. Toxin: Stx2e toxin (edema disease)
  • Lesion: Perivascular edema and neuronal necrosis. Lesions typically start within the brainstem, but cerebellar inflammation and edema is can also be present. Gastric and mesocolonic edema is sometimes viewed.
  • Clinical sign: Sudden death, eyelid edema, and diarrhea. Diarrhea is not a prerequisite for edema disease
4. Nutritional: Water deprivation (salt toxicosis), Vitamin A toxicity or deficiency, Vitamin D and/or calcium deficiency, and tremorgenic mycotoxins
  • Lesion: Water deprivation is associated with eosinophilic perivascular encephalitis. Lesions associated with other nutritional issues are often not apparent.
  • Clinical sign: Dulled mentation, seizures, incoordination, ataxia, recumbency and proprioceptive deficits
5. Trauma: Improper vaccination technique and broken bones
  • Lesion: Dependent on the type of insult
  • Clinical sign: Ataxia, paresis and prolonged recumbency are typical
Diagnostic sampling
The old adage is collect samples from “acutely affected and non-treated” animals exhibiting clinical signs that predominate within the population. This is still true in CNS disease scenarios. It also advised to submit animals in the subacute stage as some lesions, both gross and microscopic, are not always apparent in the acute cases. Your routine, complete, and clean necropsy technique, examining all organ systems will assure a proper diagnosis. Don’t just focus on animal tissues is another important piece of advice, feed could be the issue as well.
The below list is a guide to proper sampling when working up CNS cases.
  • Serum and whole blood from affected and nonaffected pigs
Reason: Serum can be useful for analyte evaluation (sodium, calcium, etc), agent and antibody detection. Whole blood may be useful to determine if the process is infectious (white blood cell count) or if toxins are a concern.
  • Brain: Fresh and formalin fixed cerebrum, cerebellum, and brainstem (PLEASE collect all, not just cerebrum)
Advice: Please try not to use captive bolt or blunt force trauma euthanasia methods in pigs being evaluated for CNS disease.
Advice: Swab the brainstem prior to brain extraction for a “clean” bacteriology sample. Sending a fresh chilled intact head is better than not submitting brain at all
Advice: Split brain longitudinally, putting the “best half” in formalin. Don’t cut into little pieces. “Bread-loafing” is encouraged
Advice: Collect proximal cervical cord as possible
  • Spinal cord: Fresh and formalin fixed 1” segments of cervical, thoracic, and lumbar cord
Reason: Pieces of spinal cord can be invaluable for diagnosis and it doesn’t need to be hard. Remove with a Barnes dehorner, cleaver, or saw. Sending intact vertebrae with the spinal cord inside is better than no spinal cord at all
  • Muscle and Heart: fresh and fixed
Reason: To rule out toxins or other diseases such as mulberry heart disease that may mimic CNS clinical signs.
  • Bone and joints
Advice: Routinely break ribs for bone strength; vitamin D, calcium or phosphorus issues. If weak or questionable, Collect rib bone which includes the costochondral junction.
Advice: Sample joint fluid, then open them (versus contaminating them first) by removing the overlying skin and using a syringe and needle
Advice: Open multiple joints, examine, and collect synovium. Submitting intact, chilled joints is an alternative.
  • A complete set of tissue; other organs
Reason: Add strength to the diagnosis and rule in/or out other issues
Reason: Need intestine to confirm Escherichia coli isolation and genotyping (edema disease)
  • Feed and water
Reason: You are there, why not collect? It doesn’t cost anything to collect 
Diagnostic testing
Diagnostic testing can be expensive with CNS like disease scenarios. The reasoning being there are numerous differentials to potentially rule out and there is not always a “PCR” for what we are trying to diagnose! Some testing modalities, especially when investing nutritional reasons, are not always clear cut with a yes or no answer either. An important aspect to bear in mind is that sample submission will drive testing; meaning that if the appropriate sample is not received, then the test will not be selected or run. Teschovirus testing is a prime example of this potential issue. If the brainstem or cervical spinal cord is not received, the likelihood of diagnosing this pathogen as the etiologic agent involved in the clinical picture is almost none.
At diagnostic laboratories, testing is highly driven off the clinical history. Yes, that means what you write on the submission form is important! This helps the diagnostician! Please be more specific that “CNS signs”. Take a moment and write something smart on the paper; if that is not an option, call.
“Routine” testing of CNS disease in the nursery pig generally involves bacterial culture of the brain, small intestine, and other major organs, and combining these finding with microscopic lesions that would be compatible with bacterial septicemia or edema disease. Microscopic evaluation would then potentially lend to further testing based on the findings. Examples include Teschovirus testing in the case of brainstem changes or vitamin D if bone lesions are viewed at the costochondral junction.
On occasion there are cases that do not align; meaning testing may be negative but there are microscopic lesions indicating a particular etiology or vice versa. In these events, further submission is recommended, but ultimately the “diagnosis” is made by you incorporating all pieces of the puzzle. 
Take home points
  1. Diagnosis of “CNS signs” is multifaceted as differentials can be vast for nursery-aged pigs and begins with a complete clinical examination. Clinical examination will aid in localizing a potentially insults or rule in/out other organ system involvement.
  2. CNS disease syndromes or like diseases require submission of multiple tissues including cerebrum, cerebellum, brainstem, and spinal cord to arrive at an accurate diagnosis. Sample collection methods and cleanliness add strength to the diagnostic findings.
  3. Diagnostic testing is driven by sample submission and reported clinical signs; Arriving to the correct etiology is based upon testing the appropriate tissue or sample and combing these with the clinical findings.
Content from the event:
Authors:
Darin Madson
Iowa State University
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