Rabies Awareness

Etiology

Rabies is neurotropic rhabdovirus that causes fatal infection in dogs, cats and humans. Usually infection is transmitted by inoculation with saliva by means of a bite. The virus then spreads into the CNS via peripheral nerves. Once the brain is infected, the virus spreads out through peripheral nerves to the salivary glands among other targets – at this point, the animal can transmit rabies.

Signalment
Any dog, cat, horse, cow, HUMAN

Clinical Signs

Two syndromes are described:

• Furious syndrome (forebrain signs)

• Paralytic syndrome (lower motor neuron signs ascending from the site of the bite).

Once neurologic signs are present, progression is rapid, and most animals will be dead within several days. Rabies should be considered as a differential diagnosis in any animal with acute onset, rapidly progressive neurologic disease especially if there is a poor vaccination history or exposure to other rabid animals.

Diagnostic Tests

Key point: Definitive diagnosis can only be achieved postmortem, and requires fluorescent antibody staining of brain tissue to demonstrate rabies antigen. A serum RFFIT (Rapid fluorescent foci inhibition test) can be performed to evaluate for evidence of previous vaccination however it should NOT be used to make a diagnosis of active rabies infection. Due to the neurotropic nature of rabies it can remain undetected by the immune system and therefore cause a negative (false negative) RFFIT antibiotic result.

Further reading
If you're interested in reading about a real case of Rabies virus infection please check out this article. https://doi.org/10.5326/0390547 I saw this case a number of years ago, but the disease hasn't changed much in 20 years! Furthermore, a rabies positive bat was identified on a sidewalk in Dane county just this week. Although fewer Rabies positive bats have apparently been identified this year (so far) the virus is still around and therefore still something we should be talking about!

Thanks for reading! Rabies virus infection is something I think about daily, given the cases that I see, and is one of the more daunting diseases we are faced with. Please reach out if you have any questions!

Other good resources:
The Wisconsin Rabies Algorithm: (for exposure or sick animals) https://www.dhs.wisconsin.gov/rabies/algorithm/algorithmcategories.htm
Illinois Rabies information: https://www.ilga.gov/commission/jcar/admincode/008/00800030sections.html

Temporalis and Masseter Muscle Atrophy

It's Tuesday at 10 am and you're about to see a 7 year old dog with unilateral temporalis and/or masseter muscle atrophy. What parts of the neurologic system could be involved?

1. Muscle: A problem with muscle function, termed a myopathy, can result in muscle atrophy. The most common cause of temporalis and masseter muscle atrophy in dogs is masticatory muscle myositis (MMM), which is caused from an immune mediated attack against the muscle fiber. This is a UNIQUE form of muscle inflammation because the proteins on these muscles are embryologically unique (2M fiber type, if you must ask) from all other muscles in the body. We care about that because it means that we can have a an antibody (AB) test that we can run that is highly specific AND sensitive! The second myopathic disease of the head muscles, that I see commonly, is myositis due to neospora or toxoplasma infection. Simply put, the protozoa get into the muscle, set up a secondary inflammation (myositis) and sometimes you can see a mild positive on the aforementioned MMM AB titer test. However, if you concurrently test for neospora and toxoplasma (serum titers) you can catch this "false" positive, and treat the correct disease.

Treatment for MMM: Immunosuppressive steroids for 30+ days
Treatment for infectious myositis: clindamycin or sulfa antibiotics until negative or stable titers.

2. Cranial nerve 5: A dysfunction of CN 5 can result in denervation atrophy of one (or both) temporalis muscles. On the exam, look closely for concurrent signs of a sensory neuropathy to the face and if present, a CN 5 dysfunction should be suspected. The differential diagnoses list is much bigger but typically centers around a few common causes (neoplasia, neuritis, hypothyroidism, and trauma). To diagnose a CN 5 neuropathy the best approach is a brain MRI followed by a spinal tap, along with titers for infectious diseases, thyroid panel and routine CBC, serum biochemistry. Not all of those tests are needed for each patient so pick and choose as appropriate for your case.

Treatment for CN 5 deficits: this varies widely and is dependent on the underlying cause. It is a bit hard to summarize TidBit Tuesday-style. :) Stay tuned for another email detailing all of the possible causes and treatments for cranial neuropathies.

I hope this TidBit Tuesday helps you focus your exam, and thoughts, when faced with a case of unilateral atrophy of the muscles of the head. This report was stimulated from recent conversations about this presentation so please reach out if you have a case, or questions about a case, with unilateral muscle atrophy. The more we talk with each other, the more we learn from each other!

Have a great week!

Traumatic Brain Injury And Blood Glucose

We're approaching the month of October - known for scary costumes and sugar overload. Why not look at a recent study about glucose to kick up our adrenaline? Okay, so this is a study in dogs and cats, specifically about traumatic brain injury and relationship between glucose and prognosis but don't shame me for trying to make a link to "current events"!

Background

This was a retrospective study (Cameron S, et al. JVECCs, 2021) looking at 131 dogs and 81 cats that were presented to one of two teaching hospitals following trauma and were diagnosed with traumatic brain injury (TBI). (TBI is the new term for head trauma, in case you're wondering.) At admission, glucose and a modified Glasgow Coma Scale, among other tests, were evaluated from the record and correlated to outcome. The animals were termed "survivors" if they lived to be discharged from the hospital and they were termed "non-survivors" if they, well, didn't.

Results

Here are the key points, and the interesting bits!

Dogs:

• The MGCS was significantly lower in non-survivors compared to survivors.

• Blood glucose concentration was significantly higher in non-survivors compared to survivors.

• A cut off of 148 had a sensitivity of 73% and specificity of 76% for a poor outcome (non-survivor)

Cats:

• The MGCS was the ONLY significant predictor of outcome

• Glucose was not significantly related to outcome!

Take home message:
When presented with a post-traumatic patient, perform a serum blood glucose concentration and a neurologic examination (to get a MGCS). Both of those may be able to help you predict the outcome for a DOG (not cat) and guide the clients towards or away from referral if they are considering humane euthanasia. Naturally, we must account for co-morbidity, financial impact and prior medical conditions of the pet when faced with a post-traumatic patient but hopefully these two little points will further improve your ability to help the patient.

Thanks for reading! I hope you have a nice week and keep those consults coming!
New hours are in effect so please use the online scheduler whenever possible to schedule a consult or email/text me if you cannot find a suitable time. Thanks!

Cluster Seizure Management

What is a cluster seizure?

Cluster seizures are defined as 2 or more discrete seizures within a 24 hour period.1 Cluster seizures are different than status epilepticus (any one seizure lasting for an extended period of time, or 2 seizures in which poor recovery occurred between seizures). Cluster seizures pose a special concern for seizure patients because of they have been linked with poorer outcomes compared to dogs without a history of cluster seizures.

The goal with cluster seizure management is to minimize the number and duration of seizures. A secondary goal is to reduce the need for hospital visit or stay thus reducing the financial burden to the client.

When should I provide a cluster seizure plan to a client?

• If a patient has a history of 2 or more times when they had cluster seizures

• If the patient has a history of status epilepticus

What drug choices, routes of administration and doses can I offer?

Levetiracetam

1. Rectal administration – 40 mg/kg PR at the time of seizure, repeated once if needed within 24 hours. Results suggest an improvement in seizure management in the medium term using rectal levetiracetam AND standard anticonvulsant therapy in one stud

2. Oral administration – start 20-30 mg/kg PO q8hr (NOT Extended release) levetiracetam after a pet experiences the first seizure and has recovered enough to eat and continue q8hr dosing for 2 days beyond the pet’s last seizure. The levetiracetam is then stopped, and standard anticonvulsant therapy is continued long-term. Clinical experience suggests this approach will reduce clinic visits, number of seizures during the cluster event. However, clinical side effects such as sedation or ataxia may be present during the dosing period. Note: This approach should NOT be used if levetiracetam is part of a patient’s standard oral therapy for long-term seizure control. Suddenly discontinuing an anticonvulsant medication can lead to breakthrough seizures or status epilepticus.

Benzodiazepine
Diazepam has been the main acute anticonvulsant treatment for veterinary patients.4–7

1. Rectal - Be sure to target the rectum, not colon, to avoid hepatic metabolism. Start 1-2 mg/kg per rectum.10 Compounded suppository formulations of diazepam have not demonstrated reliable serum diazepam concentrations in dogs therefore compounded suppositories are not currently recommended.9

2. Intranasal – preferred by some due to the ease of administration, and avoidance of the first pass effect of metabolism. Start with 0.5 mg/kg intranasal.

Midazolam

1. Intranasal – this is my preferred route and drug for at home benzodiazepine administration. Additionally, it was reported to be favorable compared to intravenous midazolam in 44 dogs. 11 Start with 0.2 mg/kg intranasal.

2. Intramuscular – this route is favored by some but is not my recommended route of administration for clients at home in emergency situations. In a clinical situation, intramuscular administration can be effective when intravenous access is limited. Starting dose of 0.2 mg/kg is recommended.

3. Rectal – do not use midazolam rectally due to erratic and unpredictable plasma concentrations at standard doses.

Phenobarbital
Patients receiving daily phenobarbital administration can benefit from an increase, or pulse, of phenobarbital therapy during a cluster event.

1. Oral increase – in my clinical practice we regularly recommend increasing a dog from q12h dosing to q8h dosing for 2 days beyond the last seizure. An example of this would be if a dog had a seizure Saturday morning. Upon recovery from the seizure an additional oral dose of phenobarbital (at the same oral dose administered) is recommended followed by q8hr dosing Sunday and Monday. Tuesday the dog would return to the standard twice daily dosing interval. This approach provides a slight increase of serum phenobarbital concentrations which may protect against further cluster seizures. Clinical adverse effects such as increased sedation, ataxia, polyuria, polydipsia, and polyphagia may become evident during the increased dosing period.

Summary
Providing options at home for cluster seizure care can reduce the need for hospitalization, or clinic visits. Additionally, any of the above treatments can be provided in hospital during seizure observation should that be needed. All the treatment choices discussed above are targeted for dogs and are rarely used in cats. Although the medications discussed have been evaluated for safety for use in cats, the specific protocols do not have clinical trial data, and minimal clinical experience.

This week I spoke to a wonderful group of vets at IVECCs about cluster buster protocols and it reminded me that we haven't read about this in awhile on our TidBit Tuesdays. We're all learning together!
(references available upon request)

Canine Cognitive Dysfunction

Cognitive Dysfunction Syndrome in Dogs

Canine cognitive dysfunction syndrome (CDS) is reported to be a progressive disorder with specific characteristics. Many authors group canine CDS signs into specific categories such as:

• disorientation

• social interactions

• sleep-wake cycles

• house soiling, learning and memory

• activity and anxiety

There is a scoring system called the DISHAA Cognitive Dysfunction Evaluation Tool that utilizes these categories in forming a score, that has been shown by some to correlate to the level of impairment of the dog.

A recent study out of The Ohio State University by Dr. O'Brian et al, published in JAVMA (Sept 15, 2021), described the use of an educational 50 minute weekly class, as a means to controlling clinical progression of CDS. This is a case-control study with about 20 owner/dog pairs completing the class and 66 owner/dog pairs used as control. Scoring was performed at entrance to the study, as well as at 3, 6 and 12 months. During class the instructor spent part of the time informing the clients about a specific aspect of CDS, and the remainder of the time working on an interactive activity with the dog/owner pair geared towards cognitive enrichment and new learned tasks. The owners were asked to practice outside of class as well as in class. The most notable finding was a significant progression of clinical score, using the DISHAA scoring system, in the control group and a lack of progression in the class group. The only exception to this was the disorientation scores. These appeared to increase in the class group which, as the authors suggested, may be due to increased owner awareness by attending the class. The authors suggest that owner information, and structured interaction with the dog, is what slowed progression of all of the other markers of CDS.

What is the take away?

Well...maybe an information session (zoom or live) once monthly for all of your dogs over age 8 could increase awareness by clients and alert them to seek medical attention should signs arise. Or, maybe a senior class in your area (lead by a veterinarian or a trainer) might be the best answer for your clientele.

I hope you have a wonderful week! Please remember that I will be closed Monday-Thursday next week, with limited hours on Friday September 10th. Have a safe and happy Labor Day and Happy New Year, if you celebrate!

Canine Distemper

Etiology

Viral replication initially begins in lymphoid tissue and induces marked immunosuppression. Virus then reaches the CNS through the choroid plexus, ependymal cells and perivascular spaces 1-3 weeks after infection by virus infected lymphocytes and monocytes. What is the significance here? Neurologic signs often follow GI and respiratory signs.

Signalment

Distemper should be strongly suspected in an unvaccinated young dog with neurologic signs and with a history of recent GI and/or respiratory disease. Myoclonus, a repetitive twitching of muscles, is a common indication of current or previous distemper infection. Distemper can also be present – and a diagnostic challenge – in older, vaccinated dogs with no history of systemic disease prior to neurologic signs. Older dogs typically have a demyelination, with chronic, slowly progressive, signs of a myelopathy.

Clinical Signs

Respiratory and GI signs occur 1-3 weeks prior to CNS signs. The presence and pattern of illness depend primarily on the viral strain and the age and the immunocompetence of the patient. (Different strains but only one serotype means that exposure to one strain protects dogs against any subsequent strain.) There are 3 different scenarios:

• Dogs that develop an early, effective immunological response recover from mild or no neurological signs. Approximately 50% of dogs have a subclinical neurologic course

• Dogs that are unable to mount an immunological response suffer severe systemic illness, including acute encephalitis, leading to death within about 3 weeks of exposure. These dogs will have seizures, blindness, and other signs of grey matter disease.

• Dogs with delayed immunologic response don’t develop acute illness but may develop a chronic, persistent infection, characterized by chronic encephalitis or myelitis.

In acute disease, infection of neurons and microglia and astrocytes leads to mostly grey matter damage. In chronic infection, the immune response to persistent viral infection leads to inflammation and demyelination. Vaccine induced distemper is associated with a mild encephalitis in dogs vaccinated with modified live vaccines.

Diagnostic Tests

• Active or inactive chorioretinitis may be evident on ophthalmoscopic examination.

• CSF varies from normal to having increased protein and lymphocytic pleocytosis during active infection

• Distemper antibody titers or PCR in CSF, blood and urine can be helpful. False positive urine and blood PCR results may occur within 3 weeks of vaccination.

• PCR on CSF is the most diagnostic test for active infection, however myoclonus, demyelination and seizures can be residual neurologic signs after the acute infection has been cleared. Therefore, a negative PCR on CSF does not suggest that the pet NEVER had distemper, it merely suggests that there isn't detectable virus at that point in time. CSF titers (IgG/IgM) can be quite useful in this situation when compared to the serum titers. That said...what do we do with this information?
  

• Immuno-histochemistry on hyperkeratotic foot pad, conjunctiva, respiratory epithelium or CSF WBC can be diagnostic.

Treatment

Supportive care is important. Anticonvulsant drugs should be employed if seizures are present. Quality of life may be limited and poor if seizures are present and progressive. Myoclonus does not necessitate euthanasia (and should be differentiated from seizures) but it may negatively affect the quality of life depending on the muscles involved. I have personally seen distemper cause myoclonus of the jaw with repeated opening and closing (it looks like a pet gasping for air), flexion of the lips (with resultant wear of the teeth due to grinding) and abdominal contraction (like a hyperactive cutaneous trunci reflex) in dogs with confirmed distemper. No treatment resolves myoclonus at this time.

Although this is a rare disease due to vaccination, we have had a resurgence in our area due, I suspect, to an increase in pet adoptions from endemic areas such as the southeastern USA. Vaccination can prevent infection for most pets!

Have you treated distemper? How did it go? Reach out and let me know if you have any questions or comments on this disease.

For those of you in my referral zone - please note that I will be closed and not responsive to email or telephone Monday-Thursday September 6-9th as we celebrate Rosh Hashanah (Jewish New Year). I apologize for any delayed responses during this time and, as always, appreciate your patience!

Geriatric Vestibular Disease

Geriatric Vestibular Disease of Dogs and Cats

Geriatric vestibular disease (GVD) is characterized by an acute onset, unilateral failure of the peripheral vestibular system. The cause remains idiopathic, but causes such as neuritis (viral or immune mediated) or atrophy have been hypothesized. A recent study (DOI: 10.1111/vru.12893) by Sungjun Won and Junghee Yoon out of South Korea identified a significant size difference in the utricle, one of the parts of the bony labyrinth in the ear, in dogs with GVD compared older dogs without GVD. Necropsy evaluation has shown a reduction in the size of the peripheral CN 8 and the affected ganglion, further supporting atrophy as a cause. And yet, it is difficult to explain the recovery that most dogs and cats experience 1-6 weeks after onset of signs.

Common Clinical Signs

Animals with GVD are middle age to older dogs and cats and demonstrate peracute onset of signs, often proceeded by vomiting with no progression after 24 hours. These dogs and cats usually have very severe vestibular signs such as head tilt, nystagmus, ataxia (if ambulatory), positional strabismus and rolling/nonambulatory vestibular ataxia. IF you are able to have the animal stand you should not find paw replacement deficits, hemiparesis or obtunded mentation. If you do, the lesion localization is central and a different set of differential diagnoses should be considered.

Differential Diagnoses for Peripheral Vestibular Disease
Not accounting for history, a general list of differential diagnoses for peripheral vestibular disease would be as follows:
Degenerative: none
Anomalous: none
Metabolic: hypothyroidism
Neoplasia/nutritional: Yes (lymphoma, nerve sheath tumor)
Infectious/Inflammatory/Idiopathic: Yes (neuritis and geriatric vestibular disease)
Trauma/Toxin: Metronidazole SHOULD be central, but it may be difficult to tell in a recumbent animal. Trauma - less common in dogs and cats.
Vascular: none.

Geriatric vestibular disease is diagnosed by exclusion at this time. Although the report referenced above does provide measurements for the utricle on MRI, it is not yet a diagnostic marker for GVD. Exclude all other causes using chest x-rays, blood work including T4, brain MRI and spinal tap if needed.

Treatment?

This is a self-resolving disease. The head tilt is commonly permanent, but all other signs of vestibular disease should resolve over several weeks. Signs begin to improve 24-48 hours after onset of signs but may take up to 1 week to show improvement. Full resolution of clinical signs should be by 6 weeks. If signs wax and wane, or progressive worsen, GVD is not the proper diagnosis. Supportive care such anti-emetics. diazepam or meclizine for anti-vertigo effects, and nutritional support such as hand feeding (only when sternal!) , may be used. IV fluids may be needed for severe or prolonged nausea.

Prognosis

Don't euthanize these pets in the first 24 hours! They look miserable...but they can recover with time and supportive care. This can be very difficult for clients to witness and, because the pets are elderly, may result in a triggered response to consider euthanasia. If you can, please hang in there for a few days even if that means hospitalization. Signs may occur multiple times over the animals' life.

Thanks for reading! This TidBit Tuesday was prompted by one of you so keep those suggestions coming! If there is something you'd like to read about, chances are that someone else is also interested too.

My hours are changing the last week of August due to school starting. As always, please let me know if you cannot find an appointment time through the online scheduler.
Have a great week!

Time for a Tongue Twister!

Signalment: 12 year old MC Mixed breed dog, 45 kg
History: 1 month history of change in bark, with a 1-2 week history of difficulty eating and drinking. The owners also identified difficulty walking in the last few days and a decrease in the dog's interaction with them.
Physical Examination: Grade II/VI left heart murmur, previously noted and not progressed. The remainder of the exam was unremarkable.

Neurologic Examination

Mentation: Mildly obtunded. The pet interacted when asked, but otherwise seemed content to stare at the floor.
Cranial nerves: Decreased to absent gag reflex, tongue atrophy (see the photo above), all remaining cranial nerves were normal.
Gait: Ambulatory mild proprioceptive ataxia in all four legs
Reflexes: Normal spinal reflexes including c. trunci and perineal.
Palpation: Non painful spinal palpation however pain elicited with cervical ventroflexion
Postural reactions: absent right thoracic and right pelvic limb paw replacement test, normal left paw replacement thoracic and pelvic.

Neuroanatomic Lesion Localization?? To do this, we need to break it down and identify all of the possible anatomic localizations each neurologic deficit could be noted. Unfortunately the table does not copy to this blog very well so please email me or join our TidBit Tuesday mailing list to get all of the details.
What I did was list all of the possible locations that the affected deficit might involve and then narrowed down the lesion localization two ways:

1. Find the common denominator. In this case, the medulla. OR

2. Find the cranial nerve(s) affected and determine if the pet also has: a) abnormal mentation, b) hemiparesis ipsilateral to the affected cranial nerve or c) paw replacement deficits ipsilateral to the affected cranial nerve. If they do, it is central. If not, it is a likely a peripheral neuropathy.

Neuroanatomic Lesion Localization: Medulla, right side.

Differential Diagnoses: Neoplasia, meningoencephalitis (infectious or inflammatory)

Case Conclusion

This dog had normal CBC, serum biochemistry, UA, chest radiographs and abdominal ultrasound. Brain MRI identified a discrete contrast enhancing extra-axial mass in the right caudal fossa affecting the right side of the medulla. This finding was most consistent with a meningioma. A spinal tap was not performed due to the proximity of the mass to the cerebellomedullary cistern. Based on the working diagnosis surgical decompression, radiation therapy or supportive care were discussed with the owners and they elected supportive care.

You may recognize this case if you have been a loyal TidBit Tuesday reader. This was repeated from February 2020 because I felt like it was a good time to review cranial nerve lesion localization with a very interesting cranial nerve deficit. Thanks for reading (again)!

I hope you have a great week!

Dysautonomia in Dogs and Cats

Dysautonomia in Dogs and Cats?

Before we dive into this topic, I wanted to report the diagnosis for the case from last week's TidBit Tuesday mailer. The cat with the C6-T2 myelopathy was diagnosed with an FCE and was managed successfully over about 2 months to an almost normal return to function.

Now, on to this week's TidBit Tuesday...

Several of us worked on an interesting case together this week that tickled my memory about a disease that we, in Wisconsin, do not see very often. I thought we could all refresh together.

Dysautonomia is (typically) caused by degeneration of the autonomic, and some somatic, nerve cell bodies throughout the spinal cord and some brainstem nuclei.
Common Clinical Signs

With this disease, you may see vomiting first, followed by dysuria (enlarged bladder that is easy to express but difficult to void by the patient). One of the hallmark signs is a loss of anal tone and THIS IS SOMATIC not autonomic. We can see a mix of lower motor neuron signs with autonomic loss in this disease! Absent PLR and elevated 3rd eyelid are common findings on physical examination. From there, you may diagnose megaesophagus and ileus on radiographs.

Diagnosis

A study by Dr. Berghaus et al in 2001 identified that dysautonomia was found more often in rural areas, with access to water or farm land. Additionally, all of the published US cases have been from Missouri/southern Illinois region.

This disease is diagnosed through pharmacological testing and elimination of other etiology. In Dr. Berghaus' study, the Schirmer tear test was below 5 mm/min in 50% (20) of dogs, between 5-10 mm/min in an 10 additional dogs. There was no response to an atropine response test in many dogs, and some response in a few cases. Finally, most dogs had a rapid response to dilute pilocarpine in the eye, but not all. All of these tests are looking at the autonomic system in different areas of the body. When a reduced response to one or more of these tests is noted, taking into account the clinical history, you may wish to consider dysautonomia as a diagnosis.

Unfortunately, there is no known treatment that will reverse clinical progression. A combined immune mediated dysautonomia, and myasthenia gravis has been reported but even these cases do not appear to respond adequately to immunosuppression. The final diagnosis is obtained on necropsy.

Although we are ending on a sour note, I hope you have enjoyed this review of dysautonomia. Please let me know if you have any questions on this case, or any other neurology case.

I love helping you, help your patients with neurologic disease!

Neurologic Cat?

Where is the Lesion?

History: Sarah is a 4 year old, indoor only FS DSH. She was obtained as a kitten and had been normal, per clients, her entire life thus far. She presented to me for acute onset (same day) weakness. No known trauma, toxin ingestion or medication exposure.

Physical examination: No abnormalities, normal TPR.

Neurologic examination:
•Mentation: BAR
•Gait: Ambulatory severe left hemiparesis with proprioceptive ataxia in all four limbs
•Cranial nerves: Normal
•Postural reactions: absent left thoracic and pelvic limbs only
•Reflexes: reduced withdrawal left thoracic limb, normal all other limbs. Cutaneous trunci absent left, normal right side.
•Palpation: Non-painful

Lesion localization? I do not see evidence of intracranial disease so automatically I localize caudal to C1. Both a front and rear leg are affect, so again, we can isolate cranial to T2. So...right away you can think left C1-C5 or C6-T2 myelopathy. Which is it? Well, the reflexes were reduced to the left thoracic limb, and the reflex arc is C6-T2, so our localization must involve C6-T2.
Up is differential diagnoses building. Here is what I came up with:
D: none, this is acute
A: None, the cat is too old for congenital disease onset signs
M: none
N: Lymphoma is possible however it is rarely acute in nature
I: Meningomyelitis (infectious or inflammatory) is possible
T: No known trauma, but cannot rule it out
V: Fibrocartilagenous embolism is highly likely due to the acute onset of signs.

Did you think of something else that I missed?
Unabashed plug for the CE August 2nd here - we will look more specifically at this case and do lesion localization in greater detail. Please consider joining us from 7-8PM. Details can be found at my website.

Diagnosis: I debated about giving this away before the talk and I have decided NOT to tell you the final diagnosis this week. I will share it on next week's TidBit Tuesday (August 3rd) so stay tuned!

Hopefully you enjoyed this case review this week. Do you have a suggestion for a TidBit Tuesday topic? If so - please send me an email. I would prefer to write about something you want to read. :)

I hope you have a great week!

How is Sleep Linked to Seizures?

I had the privilege to be involved in a prospective study regarding the effects of sleep and epilepsy. This study was published this week in the Journal of Veterinary Internal Medicine (see below for a link).

Disrupted sleep is common in human patients with epilepsy. Is the same true for dogs with epilepsy?

Dr. Starr Cameron spearheaded a study at the University of Wisconsin-Madison, and enrolled dogs with confirmed or suspected epilepsy, fit them with a FitBark(TM) the dog equivalent of a FitBit(TM) and watched their sleep patterns over 12 weeks. This study was one part of a multi-part study using the FitBark(TM) technology.

So, what is the answer?

Interestingly, a statistically significant change in sleep patterns was NOT noted. These were age and breed matched dogs, too. There was a trend toward poorer sleep for dogs receiving higher doses of bromide, but it was not noted at lower doses.

What is the relationship with sleep and seizures?

In human epileptic patients, seizures beget poor sleep and poor sleep can result in an increased frequency of seizures. This wasn't shown in our dog population, but that doesn't mean that it isn't a concern for some dogs. What do we take away from this? Keep an eye on the sleep pattern of your epileptic patients and consider sleep aids if they are restless. Oh, and stay tuned for more results looking at sleep and seizures in dogs - this is a hot area of research right now. :)
Article: https://onlinelibrary.wiley.com/share/JD24HPYCTIRKYTBVSJZA?target=10.1111/jvim.16205

I hope you have a great week! Let me know if you have an epileptic patient that needs a little extra assistance - I'd love to help!

Fibrocartilagenous Emboli

First...a Case (Details have been changed for anonymity!)

I evaluated a 3 year old MI Mixed breed dog with a history of acute onset paraparesis after chasing a ball. This dog is an athlete, and he competes at an international level. After acute onset signs, the dog was seen to gradually improve motor and coordination over about 7 days.
Neurologic Examination
Mentation: BAR
Cranial nerves: Normal
Gait: Ambulatory mild right monoparesis, remainder normal
Reflexes: normal including c. trunci and perineal
Postural reactions: absent right pelvic limb only.
Palpation: Non-painful, normal cervical ROM
Neuroanatomic lesion localization? ---> see below for the answer

Differential diagnoses: FCE, Acute non-compressive disc herniation, spinal trauma.
Due to the marked improvement, diagnostic testing such as MRI was not elected. Supportive care with physical therapy, acupuncture, and limiting jumping and other highly impactful activities was recommended. The dog continued to improve and returned to normal.

What are Fibrocartilagenous Emboli (FCE)?

As the name suggests, FCE are pieces of fibrocartilage that run amok, in this case, in the spinal cord vasculature. The material is thought to be part of the nucleus pulposus which somehow gains access to the blood supply around the spinal cord. This is very different from a typical type I disc herniation! How different, you ask? Let's compare...

—-> There is a table here but it wouldn’t copy to the website. Email me for a copy of a comparison between type I, Type II, ANNPE, AHNPE and FCE if you’re interested. (Barnes@barnesveterinaryservices.com)

Neuroanatomic Lesion Localization Answer: T3-L3, right sided.

We have had some really unusual cases this week...Keep them coming! I love working through these tough cases with you and look forward to doing so again. (The not-so-tough ones are also nice...and a nice break from the tough ones!)

Let me know how I can help you, help your patients.

Audiogenic Reflex Seizures, Anyone?

As I write this, the fireworks are blazing in my neighborhood and there is a general sense of noise in the nation. How can noise relate to seizures?

What are they?

Feline audiogenic reflex seizures (FARS) start in cats late in life (> 10 years of age) and are triggered by a sound or sounds. The seizure phenotype (appearance) has a myoclonic component, but may also have absence or generalized seizures, as well.

What causes FARS?
Any noise, but usually a high frequency sound such as clinking a spoon in a tea cup triggers the seizures. Some cats will have spontaneous seizures in addition to FARS and others will purely have FARS. If you are seeing an older cat with new onset seizures, consider having the client keep a "sound diary" for a few weeks to see if there is a correlation.

Why bother identifying this...you're going to tell me to give phenobarbital!
Au contraire mon frere! A sentinel study was published in 2017 by Lowrie, et al (https://doi.org/10.1177%2F1098612X15622806) that showed a marked improvement in cats on levetiracetam in a randomized, controlled, open-label study with phenobarbital. 100% of the cats in the levetiracetam group obtained seizure control compared to 3% in the phenobarbital group. So you're correct that I typically prefer phenobarbital for feline seizures...except for FARS!

What causes FARS?

Interestingly, the majority of cats diagnosed with FARS in the published studies have had idiopathic epilepsy with a small portion showing progressive signs suggestive of active forebrain disease (neoplasia, meningoencephalitis).

That's it for today, folks! I hope you have a safe, fun week and stay cool during this hot weather!

Seizures are GOOD thing??

Brain tumors in adult dogs are relatively common. There are two primary brain tumor types in dogs: meningioma and glioma. Glial cell tumors are further divided into 3 subtypes varying from less aggressive to more aggressive in growth with rare metastasis. These tumors typically have a shorter long-term survival compared to meningiomas and are less surgically accessible. According to a recent study, dogs receiving palliative treatment have a median survival of about 1 month, compared to dogs receiving definitive treatment. Median survival for definitive treatment was almost 3 months.

This study looked at long-term survival using the new WHO classification scheme and found several interesting findings. The one that is most clinically applicable, and interesting to our pet population, is this:

Dogs with seizures as their first sign had a longer survival, regardless of histopathologic grade, than those with other neurologic signs at onset.

What does this mean? It means that, like in humans, seizures are like a warning shot, letting the rest of us know that something isn't right in the brain and we'd better take a look! If we proceed to MRI and make that diagnosis, dogs survive longer because of early onset palliative OR definitive therapy. This is yet another reason why we really should encourage clients to pursue a definitive diagnosis (i.e. brain MRI, spinal tap) even if they wouldn't consider definitive therapy such as surgery or radiation therapy. Early, aggressive, palliative medical care may actually prolong their dog's life beyond what we might get if we waited to "see what progressed".

I hope you have a good week and look forward to working with you, and your team, soon!

The full results of this study can be found at: https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.16199?campaign=wolearlyview

Hepatic Encephalopathy - UPDATE

Hepatic encephalopathy is caused by changes in hepatic metabolism that result in neuronal damage or swelling. Clinical signs can include neurological, gastrointestinal or urinary due to the abnormal metabolites or the formation of stones. As a neurologist, I see these patients when they have seizures, changes in mentation or behavior, or other neurological signs.

The preferred treatment is surgical correction with slow closing of the offending vessel. As many of us know, this doesn't always correct all clinical signs and some dogs require life-long treatment despite successful surgical closure.
Life-long medical management must provide a high quality protein source, but yet remain a low protein diet to avoid excessive amino acids.

There was an interesting article published recently (https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.16135?campaign=woletoc) that outlined the changes in the different types of amino acids present in the body. There are two main types of amino acids that researchers watch: branched chain amino acids (BCAA) and aromatic amino acids (AAA). In normal animals, the ratio of BCAA to AAA is 3.0 to 4.0, whereas it is 1.5 in animals with a portosystemic shunt. The study goals were to evaluate what happened with the amino acids after shunt surgery.

Results

Interestingly, specific BCAA and AAA did not change a lot, nor were they all outside of the reference range to start. However, the ratio of BCAA to AAA did increase (improve) but did not return back to the normal range. Clinical improvement was noted in most of the dogs, however!

What does this mean? It means that functional recovery occurs faster than biochemical recovery and functional recovery may be more "complete". This also (probably) means that we still need to dig into the amino acids a bit more to see if there are specific amino acids to be more or less worried about.

Yes, I know, this was a very academic TidBit this week and I promised they would be clinically applicable...I'm sorry! I do try to keep it clinically relevant but every now and again I must deep dive into research with you. :)

Keep those consults coming! This has been a terrific few weeks, with interesting cases. I love working with you and your staff to help patients.

Thanks for reading and have a great week!

Update on Acute Seizure Management

"Doc, The Dog is Having A Seizure!"

No one likes to hear those words (not even neurologists). You rush into the exam room and are faced with a convulsing dog on the floor. Here is your preemptive stop and think moment (yay!):

Why do we want to stop seizures, anyway?
Prolonged seizures can result in hypertension, tachycardia, acidosis and hyperthermia with secondary neuronal cell death and hypoxia. These changes negatively affect the brain and may have systemic effects as well. The goals of acute seizure management are to stop the seizure as quickly as possible thereby limiting secondary brain and extra cranial organ damage.

Give me the "Go-To", Barnes!

Look no further than your Benzodiazepine class of drugs. Benzodiazepine drugs (Diazepam, Midazolam, Lorazepam) were introduced in the 1960s for human status epilepticus. A recent human meta-analysis identified that benzodiazepines are the “best” first line IV drugs and identified the therapeutic concentration to be between 150-300 ug/ml. To date, there have not been any veterinary studies identifying which drug is ‘best’ for acute seizure management. We’ve always used benzodiazepines so we continue to do so.

• Rectal, at home care: Home care with liquid rectal diazepam is often recommended for patients at risk for cluster seizures. Compounded suppositories are not currently recommended. Rectal midazolam and lorazepam are not! We also know that chronic phenobarbital use reduced plasma concentrations of diazepam. With this knowledge we recommend dosing rectal diazepam at 1-2 mg/kg if the patient is receiving chronic phenobarbital therapy.

• Intranasal diazepam and midazolam: Intranasal diazepam, using an atomizer, resulted in detectable levels in about 2.5 minutes which makes this drug a viable alternative for at home anticonvulsant care. Midazolam was even more rapid and had a better outcome than rectal diazepam in one study of epileptic dogs so it is currently my drug of choice for at home (or non-IV) care.

All the "cool kids" are using levetiracetam. Should I?

Well, maybe yes, maybe no. Levetiracetam is still considered a new anticonvulsant drug, however its use has been documented in veterinary medicine since 2004. It is considered a relatively safe drug, with few reported side effects. This drug is typically used as an add-on or alternative to intravenous benzodiazepine therapy for acute seizure management at doses ranging from 30-60 mg/kg IV. Adding diazepam and levetiracetam together resulted in improved seizure control in epileptic cats so this is currently my recommended way to give IV levetiracetam. (Unless diazepam is contra-indicated such as with hepatic failure.)
Rectal levetiracetam may be on the horizon according to one study in 2014. However the first sampling time was 10 minutes therefore it is unclear if this drug will be useful in acute seizure management.

Is Propofol Still Used?

Yes, but there isn't any new information. We all like shiny, new things, but propofol does have a place in acute seizure management. There are a small number of published studies addressing this use in veterinary medicine. This drug is only recommended for intravenous use. Care must be exercised when using propofol due to its respiratory suppressive effects. Occasionally, intubation may be required if apnea is encountered during bolus therapy. Propofol withdrawal may result in distal limb twitching which may be difficult to distinguish from seizure activity. Extended exposure in cats to propofol may result in Heinz body anemia therefore a CBC analysis is recommended every 24 hours during constant rate infusion of propofol with cats.

Have a topic suggestion for TidBit Tuesdays? Please reach out!

Need a consult?
Email: barnes@barnesveterinaryservices.com
Telephone: 608-597-0077
website: www.barnesveterinaryservices.com

Happy Father's Day to all of you lucky Dads! Hope you have a safe, relaxing day.

When Should You Start Anticonvulsant Drugs (and Why)?

Following the recommendations of the International Veterinary Epilepsy Task Force I suggest starting anticonvulsive drugs if a patient meets one or more of the following criteria:

• Two or more seizures within 6 months

• History of status epilepticus (one seizure longer than 5 min)

• History of cluster seizures (cluster seizures meet the definition in the first point above)

• Post ictal signs are severe (ex: aggression) or lasting longer than 24 hours.

• Seizure frequency or duration is progressing in the last 3 interictal periods. (ex: 12 months apart, then 8 months then 6 months)

Medications are selected based on the metabolic status of the patient, seizure pattern and client constraints (administration frequency, cost, bias). Phenobarbital and bromide are considered first line treatments by the IVETF and are recommended for most forms of seizures in dogs. Phenobarbital could be considered a first line drug for cats as well (Bromide is a big NO-NO for cats). The level of evidence available to make these recommendations is, at the time of writing, more complete than for the other anticonvulsant drugs. I use the following table to as a guide for starting or changing anticonvulsant drugs; hopefully you find it useful also. Remember that these are guidelines and many animals need manipulation of their seizure control life-long.

Table 1: Indications and limitations of phenobarbital, bromide, levetiracetam, zonisamide and gabapentin as first line anticonvulsant therapy.

PhenobarbitalBromideLevetiracetamZonisamideGabapentinIndication (Dog)Generalized tonic, clonic seizuresFocal or cluster seizuresReactive seizuresGeneralized seizuresInfrequent statusIndication (cat)Generalized, focalnot recommendedReactive seizures, orofacial seizuresLimited data. Consider for generalized?Very little data. Consider as last choice.limitationsAnimals with hepatic disease should not use this drug.Give with care for dogs with renal failure, or renal tubular acidosis (or with zonisamide)Chronic administration may result in honeymoon effectDo not use in cats or dogs with known sulfa hypersensitivity, or liver diseaseNone known

Whew, it's hot out here! I hope you are staying cool, safe and enjoying this blast into summer.

My summer 2021 hours have started! Please email me if you have a case to discuss, cannot find a time on the scheduler for a consult, or just like to chat about all things neurology. :)

I look forward to working with you, and your clients and staff, soon!

Tetanus and Dogs

What is tetanus?

Tetanus is caused by the Clostridium tetani bacteria which produces a neurotoxin that causes muscle contractions. This bacterium is found commonly in soil and is ubiquitous throughout the world. After the bacterium is injected into an anaerobic environment it produces the toxin. The toxin targets inter neurons in the spinal cord, inhibiting their function.

Diagnosis?

A diagnosis is made by observation of classic clinical signs such as limb rigidity, muscle retraction on the face or periocular. Detection of the C. tetani bacterium in the wounds through culture can provide a definitive diagnosis, if obtained.

Treatment?

Wound debridement followed by appropriate antibiotics (penicillin or metronidazole) will result in recovery for the majority of dogs and cats. For severe cases, respiratory assistance with a ventilator, sedation to avoid painful sustained muscle contractions and 24-hour nursing care may be needed.

Seasonality?

An interesting article came across my view recently that identified a spike in tetanus cases in the winter months (December-February) in England. This was surprising because more cases are reported in warm, humid climate than cold ones. The authors didn't provided substantial reasoning for the odd seasonality but suggested it may be related to the exposure by walking in wet muddy environments. Here is the link to the article if you'd like to read more: https://doi.org/10.1111/vec.13068

I hope you have a wonderful, productive, safe week and I look forward to working with you soon. Thanks for reading!

Isoxasoline Flea Treatment and Seizures

Recently published data (2020) suggests that adverse events (AE) - the new word for side effects - are higher than reported by the manufactures of isoxazoline flea treatments. Specifically, researchers looked at Bravecto (fluralane), Nexgard (afoxolaner) and Simparica (Sarolaner) in both the US and Europe.

What did they find?

This is a TidBit Tuesday-style abbreviated summary. For the full report see the link at the bottom. There is a lot of data in this report!

• The survey (called Project Jake Survey) had 2751 respondents. It was compared to the data requested of the FDA and the EMA (European Medicines Agency).

• Almost 69% gave Bravecto, 26% gave Nexgard and a small 5% gave Simparica.

• Overall, 66.6% of dogs had a reaction to treatment

• Of the 911 dogs getting Bravecto, 791 had an AE (86.8%)

• Of the 342 dogs getting Nexgard, 235 had an AE (68.7%)

• Of the 72 receiving Simparica, 44 had an AE (61.1%)
  

What about seizures??

Death and seizures were a focus for this report, however other side effects are certainly noted and were reported. I will focus on seizures.

FDA report: Overall, 5.34% of dogs experienced seizures

• 20% of dogs receiving Simparica

• 2.8% of dogs receiving Bravecto

• 6.9% of dogs receiving Nexgard

EMA report: Over all 30.3% of dogs experienced seizures (!!)

• 60.2% of dogs receiving Simparica

• 18.7% of dogs receiving Bravecto

• 46.69% of dogs receiving Nexgard

Project Jake Survey:

• 4.5% of dogs receiving Simparica

• 14.8% of dogs receiving Bravecto

• 12% of dogs receiving Nexgard
  
  

Why are the numbers SO MUCH higher in the EMA?

Perhaps it is related to genetics in the dog population, better reporting habits, or reporting by vets vs owners (or vice versa). That question wasn't answered in the report. The take home message for me was that Simparica is blowing things out of the park with seizures but that the other two still have a substantial group of dogs with seizures as an AE.
Critically, this report did NOT state if the dogs had ever had seizures prior to administration of the drugs. They did state that at least some of the dogs had novel seizures after administration of one of these drugs...but alas we don't know the details on this.

When do the majority of Adverse Events occur?

Within the first 24 hours. These are supposed to be insect specific GABA mediated chloride channel blockers that are distributed around the body in the first 24 hours so it isn't surprising that this is the highest spike of possible toxicity to the dog. Also, AE were reported as a small spike between 8-14 days.

So, what is the take away?

• Any of the drugs in this report (Bravecto, Simparica or Nexgard) can have seizures as a side effect. Are they a cause of seizures? I'd say probably yes, for at least some of the dogs. Perhaps they lowered the threshold in prone animals too?

• It looks like Simparica may have a higher incidence of seizures

• If a dog has a FIRST seizure (within 24 hours or at 8-14 days) after using an isoxazoline drug, discontinue use and try a different class or different drug in this class.

Link: https://onlinelibrary.wiley.com/doi/epdf/10.1002/vms3.285. Publication date 2020. This was a very interesting read and eye opening for me.

Keep those consults coming! The more we work together, the more we learn from each other.

This TidBit Tuesday grew from a recent spike in questions about flea/tick medications from some of YOU...so, thank you!

I look forward to working with you and your staff, soon!

NSAIDs vs. Prednisone...What Do I Do??

Case 1: A 4 year old Dachshund with 3 day history of back pain. On neurologic examination you find spinal pain at TL junction with reduced paw replacement in both pelvic limbs, normal reflexes and normal gait analysis. Neuroanatomic lesion localization (NALL): T3-L3 myelopathy
What would you rank for a differential diagnoses list?
I'd consider IVDH, meningomyelitis, discospondylitis and neoplasia.

Case 2: A 1.5 year old FS Cavalier King Charles spaniel. On neurologic examination you find moderate cervical spinal pain with reduced paw replacement in the left pelvic limb and marked phantom scratching at the neck when lightly stimulated.
NALL: C1-C5 myelopathy
What differential diagnoses would you consider for this case? I would suspect syringohydromyelia first, followed by less likely meningomyelitis and IVDH.

Case 3: A 2 year old MC Labrador with lumbar pain, a normal neurologic examination and fever of 102.0F.
NALL: Lumbar pain (You cannot have a NALL without neurologic deficits!)
What is your differential diagnoses list for this patient? I'd consider discospondylitis, type II disc herniation, and some non-neurologic causes such as musculoskeletal injury or joint infection. Rarely we see referred pain from prostatic disease (cysts, neoplasia, prostatitis).

We know we need anti-inflammatory medication for pain management, right? Which one?

Case 1: The risk is low for infectious disease in this patient. For confirmed IVDH, neither prednisone or an NSAID has been shown to be superiors for pain control. Without a confirmed diagnosis, we must treat for the top 1-2 differential diagnoses, right? I typically start with NSAID therapy for these patients and if they are unable to proceed with MRI/spinal tap to obtain a definitive diagnosis and clinical signs of pain persist, I switch to prednisone after an appropriate washout period. Is it wrong to start steroids? No. The side effects of GI upset, ulceration and mild immune suppression make them less desirable when treating IVDH but they are not contraindicated.

Case 2: This case has a high likelihood of Syringohydromyelia (SHM) based on the breed and clinical signs. SHM has a high amount of neuropathic pain, which can be mediated by COX-2. Therefore, NSAIDs that target COX-2 may provide some relief. That said, steroids mediate sympathetic pain, decrease substance P expression and decrease expression of lots of inflammatory mediators and may decrease CSF production to boot. Therefore, with a low infection likelihood in this pet and high likelihood of SHM, prednisone is my drug of choice over NSAIDs. If you haven't confirmed the diagnosis, however, it is worth a discussion about the possibility of worsening clinical signs and the side effects of steroids prior to starting the drug.

Case 3: This dog has a high risk of infectious disease based on breed, age and clinical signs. Therefore, in addition to taking radiographs to try to find this dog's discospondylitis (!!), I would NOT use prednisone in this patient. NSAIDs provide wonderful bone penetration and excellent periosteal block of COX-2 mediated pain and would be my drug class of choice.

Steroids, especially prednisone, are not evil and they have a time and a place in neurology. (Understatement of the year😂 ) However, they have a greater chance of adverse clinical adverse effects than NSAIDs therefore they are not needed for every patient with spinal pain. Develop a differential diagnoses list that fits your patient before deciding between NSAIDs and prednisone. Still not sure? Call/email me to discuss your case, or set up a neuro consult!

Heads up - I will be on vacation May 29-June 5th and will have limited telephone and email access. I will respond to emails as I am able but will not be as prompt as usual. Please plan to schedule consults around this window as well. Thanks for your understanding, and support of my small business. I look forward to working with you soon!