Neospora in Adult Dogs

Neospora has become increasingly common in veterinary neurology, especially in the last few years. Neospora is an obligate intracellular parasite that causes notable complications in cattle but is not commonly diagnosed in dogs. Dogs are a definitive host, which means upon infection, they will not pass this infection along to other hosts (unless that new host consumes their meat). In other words, do not eat a dog infected with Neospora (!!).

How do dogs  get infected?

The most common transmission is transplacental or juvenile onset neosporosis. Dogs that develop clinical signs at greater than 12 months of age probably have adult onset or the newly acquired form. This form has fecal/oral transmission.

What are the clinical signs of Neosporosis in adult dogs?

There are two forms of disease, which may occur separately or concurrently. First, we can see neuromuscular disease. Signs may include a strict myopathy (difficulty opening the jaw, tetraparesis with normal reflexes), neuromyopathy (myopathy signs plus patchy reduced reflexes) to a full neuropathy (reduced reflexes in multiple limbs along with clinical weakness). The other option is CNS signs, for which cerebellar signs and seizures predominate.

How is it diagnosed?

Adult onset, or acquired neosporosis, is diagnosed via IFA titer. Different papers have listed different “positive” IFA titers. A recent article from Sydney Australia by Kennedy et al(DOI: 10.1111/jvim.17219), listed the positive IFA titer as 1:800. Previous studies have listed anything from 1:200 to 1:800 as the positive titer rate. I typically recommend retesting if you get anything over 1:200. If it goes UP or remains above 1:400 it is likely clinically active and warrants treatment (if clinical signs are present). PCR inconsistently diagnosed Neospora in the recently published study.

How is it treated and do relapses occur?

The first line treatment for most studies is clindamycin (median dose 15 mg/kg PO q12h) x 12-17 weeks. Sulfa antibiotics are the second line of treatment, and several dogs received both drugs in the recently published study. Prednisone is important during active CNS disease to minimize the secondary inflammatory reaction during protozoal die-off. The dose and duration of prednisone is variable, but immunosuppression should be avoided. Relapses were common in the most recent study (9 relapses occurred in 4 dogs) highlighting the need for either longer treatment, or prompt treatment if signs recur. All signs were similar to the initial presenting signs except for one dog.

Take home message?

Remember to test for Neospora caninum when presented with a dog with CNS signs, myopathy, or neuromuscular signs. A simple titer using IFA is the best step, followed by consultation with your local neurologist.

Thanks for reading! I hope you have a wonderful start to November and look forward to working with you soon.

The Case of the Shrinking Head

Signalment: 4.5 year old MC Shepherd Mix

Clinical history: The dog had a 3 week history of left unilateral temporalis muscle atrophy when I met him. Hyporexia and nasal hemorrhage from the right nostril were noted when the signs first started, but they had improved by our consult. The atrophy, however, continued to progress.

Physical and Neurologic Examination:
The physical exam was normal.

Mentation: BAR
Cranial nerves: moderate left temporalis muscle atrophy, otherwise normal. No sensory abnormalities noted.
Gait: Ambulatory, no evidence of lameness, weakness or ataxia
Reflexes: normal all limbs
Postural reactions: Normal all limbs
Palpation: Non-painful spinal palpation and normal CROM

Neuroanatomic Lesion Localization?
Let's walk this through. First, what nerve innervates the temporalis muscles? (CN 5: trigeminal) So, our problem is a) peripheral trigeminal b) brainstem at the trigeminal motor nucleus or c) muscle. How do you sort between these? Right! Let's rule out the easy one first. Signs of brainstem disease include changes in mentation, paw replacement deficits (ipsilateral to the atrophy) and/or hemiparesis. Any one of these three abnormalities is present and voila! it is a brainstem lesion until otherwise discovered. We ruled out brainstem disease in this dog. Is this, then, peripheral trigeminal nerve (motor portion) or muscle? This differentiation can be hard on the neurologic examination so I actually included both of these possibilities on this dog's final neuroanatomic lesion localization. However, without a sensory deficit (he didn't have one) a trigeminal neuropathy is less likely. That said, if the CK is normal, it's hard to make a story for a myopathy. His was normal. So...I left both on the final list. You could have said "neuromuscular" and you would have been correct because that localization includes peripheral neuropathy, neuromuscular junction and myopathy.

Differential Diagnoses?
Neuropathy: Neoplasia, neuritis (infectious or non-infectious), hypothyroidism and trauma.

Myopathy: Masticatory muscle myositis (3M), infectious myositis (toxoplasma and Neospora caninum are most common causes of infectious myositis.)

Diagnostic Results
CBC, serum biochemistry: unremarkable.
T4: normal
Neospora antibody M titer: > 1:200 (positive!)
Toxoplasma IgG/IgM titer: Negative
3M antibody titer: < 1:100 (negative)

Conclusion
This patient was diagnosed with a Neospora myositis based on positive titers. We placed him on sulfa antibiotics and tracked the titers. Clindamycin is also an acceptable antibiotic choice for fighting protozoa myositis.
2 months later: 1:200
4 months later: 1:100
1.5 months later: negative.

Unfortunately, this patient developed an adverse reaction from the sulfa that included blood dyscrasias and hypothyroidism 5.5 months from the original diagnosis. The sulfa-based antibiotic was discontinued and clindamycin was started. My goal is to have 2 negative Neospora titers before discontinuing antibiotics but we will have to see if we get to meet that goal with this guy!

Key Points:
1. Muscle atrophy (especially unilateral) should prompt a toxoplasma (cat) and toxoplasma and Neospora titer (dog). This is a lesser known infection in Wisconsin dogs!
2. Treat with either a sulfa antibiotic or clindamycin to the point of two consecutive negative titers to ensure clearance of the infection. Titers are typically checked every 4-8 weeks.

This was a very interesting case and a great one to remind us all about protozoal infections in house pets. Remember - when we work together, we all learn!

I look forward to working with you soon.

Neospora Meningoencephalitis vs Immune Mediated Meningoencephalitis

Immune mediated meningoencephalitis (aka meningitis of unknown origin: MUO) is very common and is a cause of intracranial disease for many pets. Infectious meningoencephalitis accounts for only about 2% of the cases seen through a referral center and is, therefore, in the minority. Infectious meningitis may be secondary to fungal infection, protozoal (Toxoplasma or Neospora), viral, bacterial or in southern states, some tick borne diseases. Neospora infection is one of the more common causes of infectious meningoencephalitis we see in Wisconsin (probably second only to fungal) and therefore one of the main differential diagnoses for a pet with meningoencephalitis. The current way to diagnose Neospora is via serum titer elevation, evidence of encysted protozoa on biopsy or necropsy, or PCR on serum or CSF. All of these tests take a variable amount of time, depending on the laboratory, so some researchers in the UK came up with another idea. (https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvim.16334)

Scientific Question: Can we differentiate between Protozoal meningoencephalitis and MUO using CK and AST values?

Rational: Protozoa (Toxoplasma and Neospora) are often found in muscle which would result in membrane disruption, thus elevating CK (and subsequently AST). Seizures, a common sign of MUO and protozoal meningoencephalitis, can also elevate CK so the researchers also aimed to evaluate the temporal relationship between seizures and CK elevation.

Methods: This was a retrospective study of 59 dogs diagnosed with MUO and 21 dogs diagnosed with Neospora (no dogs were diagnosed with Toxoplasma in this study).

Results: A significantly higher CK and AST value were identified in dogs with Neospora compared to those with MUO. Using a cutoff value of 458 U/L, there was a sensitivity of 95.24% and specificity of 96.61% for active Neospora meningoencephalitis and using a prevalence of 2.25% for active infection in the UK, there was a negative predictive value of 99%. This suggests that dogs with a CK less than 485 U/L are unlikely to have a diagnosis of Neospora infection associated with their intracranial signs. Twenty of 21 dogs with Neospora had CK higher than 485 U/L, and 2 dogs with MUO had CK > than 485 U/L in this study.

Things to remember: CK has a short half-life (22 hours) so if you test, do so within the acute phase of disease. CK and AST are not muscle specific and can be found in myocardium, intestine and AST in the liver also.

What do you do with this information? If you have a dog with suspected meningoencephalitis, consider running a CK and AST on initial blood work. If it is greater than 485 U/L, a Neospora titer should be performed.

Have a great week and thanks for reading!

Note about the holidays: I will be available for emergency cases on December 24, and 25th.

New Years Eve and Day, I will be spending time with my family building a colossal gingerbread house and stables. If I'm not baking, cutting and cooling gingerbread I will be making sticky frosting glue and won't be available for phone calls, texts or email. Thank you for your understanding!

Neospora caninum: Update!

Medical Review: Neospora Myositis

You might be wondering why on Earth I'm talking about Neospora as a small animal vet. (Neospora causes abortion in cattle!) It infects dogs too!! Some of you have seen some positive cases with me throughout 2020 so, I thought it was worthwhile doing a mini-review so we could all brush up on it together.

Etiology: Toxoplasma gondii and Neospora caninum may cause myositis, peripheral neuritis or CNS meningoencephalitis.

Signalment:

Breed: any
Age: may be acquired in utero leading to signs at a very young age (months), or by consuming raw or under cooked meat causing signs at any age. **Adult onset is what I see most commonly. However, the dog pictured above was a puppy that presumably acquired it in utero.

Clinical signs: Stiff gait, muscle pain (myalgia), muscle atrophy. Note: Muscle atrophy can be anywhere including the muscles of mastication. I have been tricked into thinking a dog has MMM when in actuality it had Neospora myositis causing unilateral muscle atrophy in the masticatory muscles.

Diagnostic tests: IFA > 1:200 for Neospora caninum is consistent with an infection, however documentation with a repeated titer is recommended as a confirmatory test. Muscle biopsy showing the encysted organism is definitive but obviously the most invasive route.

Treatment options: Sulfadimethoxazine/ormetoprim (15 mg/kg PO q12h) or clindamycin (10 mg/kg PO q12h) twice daily is recommended for 4-6 weeks, possibly longer. Be aware that sulfa antibiotics can cause idiosyncratic myopathic drug reactions too!

Prognosis: Good, if treatment is started before severe muscle atrophy or fibrosis is present. Prognosis is poor if clinical signs are severe, or chronic.

Frequency: Uncommon, but not unheard of!

Voila! TidBit Tuesday-style update on Neospora caninum. 😊

Final question: When do I run the IFA? Answer: Any dog with a history of muscle pain, muscle atrophy (not explained by neuropathic disease) or an elevated CPK should have a Neospora titer performed. This disease is sneaky so I err on the side of caution and suggest running the test rather than getting caught unawares.

Be safe, be strong and keep those referrals coming!
Heads up for those of you in my referral area: I will be closed Thursday January 28th to celebrate my youngest kiddo turning 5 years old. My, how time flies! I apologize for any inconvenience this may cause and look forward to consulting with you on another day!