Rabies : It's still out there

I read some sobering data recently, produced by the CDC, pertaining to Rabies. They published a table of Human Rabies virus infections in the USA and Puerto Rico between 2000-2022. No cases were reported in 2022. Over the remaining 21 years, 57 cases were identified ranging in age from 7 to 87 years old. The source of infection was listed as "contact", "bite", "unknown" or "organ transplant" (Yeah, this one was unexpected to me!). One individual survived but the remaining 56 cases were, not surprisingly, all fatal. Reading this table reminded me that we haven't talked about Rabies on TidBit Tuesdays for awhile (actually since 2022!). As your friendly neighborhood neurologist, I feel strongly that we should have this conversation so please read on. 

Etiology

Rabies is a neurotropic rhabdovirus that causes fatal infection in dogs, cats and (usually) humans. Infection is caused by inoculation from saliva by means of a bite.  The virus then spreads into the CNS via peripheral nerves.  Once the brain is infected, the virus spreads back out through peripheral nerves to the salivary glands – 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). This means a paraplegic dog could be considered for rabies observation if they are NOT vaccinated. Be aware! 

Once neurologic signs are present, progression is rapid, and most animals will be dead within several days. Most of the individuals on the CDC table were deceased within 3 weeks of their noted infection date. 

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 wild animals.

Diagnostic Tests

  Key point: A 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. One of the cases I evaluated had a negative RFFIT test and was confirmed to have the rabies virus on necropsy. Due to the neurotropic nature of rabies it can remain undetected by the immune system and therefore cause a negative (false negative) RFFIT result.

What do you do if you've been exposed? Contact your local heath department immediately. 
What do you do if you have a patient that you suspect has a rabies virus infection? Contact the State Veterinarian (Dr. Yvonne Belay at 608-516-2664)

Further reading
If you're interested in reading about a 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!

Thanks for reading! A rabies virus infection is something worry about for those of you out there on the front lines. Be aware, be cautious, and when in doubt - put on PPE!! 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

Shock Index and Head Trauma

How many of you see pets with head trauma in your practice? Okay, that’s good. There are several ways to look at prognosis following head trauma but the key feature of any of the measurements is serial evaluations. One singular measurement doesn’t seem to correlate well with prognosis in such a dynamic disease. A recent retrospective study evaluated the shock index (heart rate divided by systolic BP) to determine the correlation with mortality in a population of dogs with head trauma. A second part of the study was to determine if it was predictive of survival to discharge or improvement in signs during hospitalization.

Results

 A total of 86 cases and an unknown number of control dogs (normal dogs) were included. There was quite a list of possible ways these poor dogs were traumatized and an even longer list of breeds affected. See the study for full details on that.  The mean SI for the control group was 0.75 (range 0.62-0.92 with not normal distribution). The mean SI for dogs with head trauma was 0.91 (range 0.34-3.33, also not normally distributed). SI was significantly (0.0014) higher in the trauma group compared to the control group. However, the SI was not significantly different between dogs that diet or were euthanized compared to those that lived until discharge. There was also no significant difference in SI between dogs with a normal neurologic examination at discharge and those that were improved or static, but not normal, at discharge.

So, what does this tell us? My take away is that the SI is higher in dogs with head trauma, but it doesn’t prognosticate (using the data from this cohort of dogs) regarding survival or neurologic outcome. Why is SI higher in pets with head trauma? Following trauma, if the intracranial pressure (ICP) goes UP (hemorrhage, edema) the mean arterial BP goes up to keep blood flowing to the brain. The HR will concurrently drop due to a feedback loop. This SHOULD result in a lower SI (HR/systolic BP). The authors noted that in one case they had a dog with significant hypovolemia at the initial evaluation which resulted in a very high SI but due to a swing in pressure dynamics in the brain, the dog oscillated between hypo and hypertension over time. The authors suggest that SI may be an unreliable measurement in post-head trauma patients for this reason. So, I return to all of you smart people out there. Why is the SI higher in head trauma than in control dogs? This has also been reported in humans post head trauma so there must be a very good reason, but I can’t figure it out and would love your thoughts!

Thanks for reading this TidBit Tuesday! I hope you have a wonderful week and look forward to seeing you soon!

Reference: McConnell BM, Cortes Y, Bailey D. Retrospective evaluation of shock index and mortality in dogs with head trauma (2015-2020): 86 cases. DOI: 10.1111/vec.13411

What is Cognitive Dysfunction in Cats?

Almost twenty years ago when I left my residency and started out as a newly minted neurologist, feline cognitive dysfunction syndrome (CDS) was not on my radar. That has changed. As we learned more about aging in cats, CDS has become a more recognized disease by yours truly, as well as many others. If you're like me and need a Tidbit-Tuesday style refresher...read on!

What is cognitive dysfunction syndrome?
Cognitive dysfunction syndrome (CDS) is a term used to describe deterioration of mental capabilities associated with age.  Clinical signs of cognitive dysfunction can also be associated with other age-related illnesses (e.g. osteoarthritis, structural intracranial disease such as neoplasia, or cardiovascular disease) which makes it difficult to diagnose. See table 1 for an outline of behavior changes seen in cats with CDS.
The underlying etiology of CDS is yet unknown. Causes such as oxidative stress/damage, neurodegeneration  and vascular changes are among the leading hypothesis for human and canine CDS, and therefore suspected to be similar in feline CDS.  Deposits of extracellular B-amyloid and intracellular accumulation of microtubule-associated protein tau have been seen in human patients with cognitive dysfunction. Similarly,  B-amyloid deposits and increased tau have been detected in aged cats with cognitive decline, however the significance remains unclear. 

What are the clinical signs of cognitive dysfunction in cats?
There is a handy article, published in the Veterinary Clinics of North America in 2020 by Dr. Miele and associates that echoes what others have been reporting in a very concise little table. (See reference at bottom) I have replicated this table, with a few modifications, here. Note: There are other signs such as decreased appetite or thirst, that don't usually drive an owner or veterinarian to seek consultation from a neurologist so I haven't included them here. 

Table 1: Clinical behavioral changes associated with CDS in cats.Increased vocalization, especially at nightAltered social interaction and relationships, either with other or other pet. Altered sleep/wake patterHouse soilingSpatial Disorientation or confusion (i.e. forgetting the location of the litter box)Temporal disorientation (i.e. forgetting if they have been fed)Altered activity (i.e. aimless wandering)AnxietyLearning and memory dysfunction

How is CDS in cats diagnosed?
Oh, this is as tangled of a web as the tau proteins we chase. (A little CDS humor here...the tau proteins can cause the "tangles" seen in human CDS!). Currently, the diagnosis is made by ruling out structural brain disease and systemic causes for diseases that mimic CDS. This may include complete blood count, full biochemistry panel including thyroid screening, urinalysis, chest radiographs, blood pressure assessment, brain MRI and possibly a spinal tap. Imaging changes associated with canine CDS include increased depth of the sulci, dilation of ventricles secondary to neuronal loss (called ex vacuo hydrocephalus) and a measurably small interthalamic adhesion. Exclude everything else, and it's probably CDS.

How can we help these cats age easier?
Currently, there are no proven treatments for feline CDS.  The addition of antioxidants (B vitamins, vitamin C, other) as well as fish oil were evaluated for use in cats in one study and showed promise. The use of S-adenosyl-L-methionine (SAMe) has been recommended for cats based on a study that identified improved performance on cognitive testing. This study only found significant improvement in cognitive function testing in the least affected cats. In addition to medical management, environmental management with ready access to food, water, litter box and areas of comfort (beds, hiding spots) is recommended. Environmental stimulation with low impact toys, or bird feeders in which the cat can choose to ignore any activity if they do not feel inclined to engage, are recommended. Finally, focused veterinary visits can be important for cat owners to feel supported through the aging process. Focus your exam to specifically evaluate body weight, urine production (to assess for signs of dehydration), behavior changes and mobility.This may help detect signs earlier in the course of disease and to identify concurrent morbidity that may contribute to, or be confused with, cognitive dysfunction.

Did I forget anything? Most of you treat and see this more than I do. What have you used (successfully, or not) for treatment? 

Reference:
Miele A, Sordo L, Gunn-Moore DA. Feline Aging: Promoting Physiologic and Emotional Well-Being. Vet Clin North Am - Small Anim Pract. 2020;50(4):719-748. 

Global brain ischemia

A recent article by Dr. Harper Crawford and colleagues from the UK caught my attention. Global brain ischemia can be seen following minutes of poor blood flow including during cardiopulmonary arrest during general anesthesia, severe bite injuries and strangulation. It has also been associated with the use of mouth gags during dental procedures in cats. (Yikes! You probably knew this, but I was surprised by this!) This article was an enlightening review of global brain ischemia as well as a retrospective look at several cases with a focus on treatment, survival and prognosis. 

What is the consequence of failure?

The authors suggest that cerebral perfusion failure can simply be defined as failing to meet the energy demands of the brain and failure of adequate waste removal products. Simple, yes? Irreversible failure can start within minutes of ischemia through loss of ATP. After ATP is depleted, Na+ and K+ will influx intracellular dragging water with it and the neuron will depolarize. This is the start of cytotoxic edema. From there, a secondary release of excitatory neurotransmitters, particularly glutamate will be released which results in eventual mitochondrial dysfunction, lipid peroxidation and vascular injury. The final nail in the proverbial coffin is rising intracellular Ca++ which triggers cell death. The most sensitive cells are in the cerebral cortex, hippocampus and Purkinje neurons in the cerebellum.

Materials and Methods

Short term outcome was defined as survival (or not) for the first 72 hours. Long-erm was defined as the neurologic examination at the last follow-up examination available for review.
The study utilized an outcome scale as follows:
0: dead or euthanized due to severe neurologic deficits
1: poor recovery with severe persistent neurologic deficits
2: good recovery with mild persistent deficits
3: excellent recovery with normal function.

Results

10 animals were included: 8 dogs and cats with in hospital cardiopulmonary arrest and 2 dogs with out of hospital arrest (1 vehicular trauma, 1 asphyxiation from food). The duration of suspected arrest ranged from 1-5 minutes (median 3 minutes) for animals with in-hospital cardiopulmonary arrest and 10-22 minutes for the 2 animals with out of hospital cardiopulmonary arrest. The neurologic exam for the animals with in hospital cardiopulmonary arrest was reported at a median of 9 hours post insult. Median hospital duration was 7 days. Short term survival occurred in 8/10 cases including 1 case that did not survive to long-term. Seven animals survived to discharge and were re-evaluated at a median of 67 days. Outcome scale results:
Grade 0: 3
Grade 1: 1
Grade 2: 2
Grade 3: 4
The patients with an outcome score of 2 or 3 all showed consistent neurologic improvement in the first 48-72 hours. For the animals that experienced seizures during hospitalization (3), anti-epileptic medication was continued for between 2-8 months after starting. Levetiracetam was used in 1 cat and 1 dog, and phenobarbital was used in 1 dog. No additional seizures were reported in any pet following discharge.
This report demonstrated that although global ischemia can cause severe neurologic deficits, successful long-term outcomes are possible. Furthermore, they noted that an association with duration from onset of cardiopulmonary arrest to spontaneous breathing is a factor in recovery in rodent models and human studies, but this study was too small to draw those conclusions.

References: DOI: 10.1111/jvim.16790 Harper Crawford A, Beltran E, Danciu CG, Yaffy D. Clinical presentation, diagnosis, treatment and outcome in 8 dogs and 2 cats with global hypoxic-ischemic brain injury (2010-2022). JVIM 2023.
Thanks for reading! I hope you have a great week and I look forward to working with you soon!

Pituitary Apoplexy in Dogs

Pituitary Apoplexy in Dogs

What is Pituitary Apoplexy and What Does It Look Like?
Pituitary apoplexy is a clinical diagnosis caused by acute hemorrhage or infarction of the pituitary gland. The hemorrhage occurs secondary to neoplasia (benign or malignant). The hemorrhage is thought to occur because the tumor grew faster than the blood flow, or because of compression of the very sensitive blood vessels in the area of the pituitary gland.  Apoplexy isn’t common with pituitary neoplasia, and rarely fatal, but remains an important possibility for patients with pituitary gland neoplasia. Clinical signs described on presentation for dogs with pituitary apoplexy include acute onset mentation changes (obtunded, stupor, coma:62%), cranial nerve deficits (65%), gastrointestinal signs such as vomiting or nausea (54%), gait changes such as circling, weakness/paresis, ataxia (85%), and hyperthermia (31%). Other signs such as bradycardia, and cervical hyperpathia were noted but less commonly. The GI signs are critical, and unique, and shouldn’t be ignored. They could be due to vestibular signs (present in about 15% of dogs), but also could indicate a rapid rise in intracranial pressure.
Do all Dogs with Pituitary Apoplexy have Endocrinopathy?
No! According to a recent study by Woelfel et al, only 50% of dogs with pituitary apoplexy diagnosed on either post mortem exam or presumptively diagnosed on MRI had an endocrinopathy. A further 12% had signs suggestive of an endocrinopathy but did not undergo workup. This means that 38% of dogs did not have clinical or biochemical evidence of an endocrinopathy. The endocrinopathies could be the obvious one (Cushing’s disease), or the less obvious (central diabetes insipidus, hypothyroidism).
Treatment and Survival
Dogs receiving radiation therapy survived longer than those medically managed. There is probably a bit of bias, however, because the severity of clinical signs likely steered clients or veterinarians towards or away from treatment. The use of hyperosmolar solutions (mannitol, hypertonic saline) was associated with a poorer survival. Again, this may be due to the severity of signs of those patients receiving this treatment rather than the treatment itself. No clinically useful markers were identified to predict survival in this study but that doesn’t mean they don’t exist; just stay tuned!
Take home message: Acute onset mentation changes with vomiting? Get those dogs to a neurologist (or get a consult!!) as soon as you can.

I hope you have a wonderful week! I look forward to seeing you soon!
 

Reference: https://doi.org/10.1111/jvim.16703

Neurologic signs of Hypertension in Cats

Hypertension is common in cats. It can be associated with a predisposing disease such as chronic kidney disease or hyperthyroidism, or idiopathic. Idiopathic hypertension is diagnosed when all predisposing causes have been eliminated (and hypertension is documented on 2 separate occasions)  and accounts for less than 1/2 of the cats diagnosed with hypertension (about 40%). 

Target organs for hypertension are the CNS, kidneys and cardiovascular system. Despite under recognition by clients, several studies have suggested that hypertensive encephalopathy might be present in 30-40% of cats. 

Neurologic manifestations of hypertension in cats

Seizures, mentation changes, vestibular signs (central), behavioral changes (disorientation), tremors, sudden collapse, cervical ventroflexion, paraparesis, cerebellar ataxia with hypermetria, cranial nerve deficits and cortical blindness (not retinal blindness). That's quite a list, isn't it?? It's amazing that these signs are the reason for presentation to a vet in only 10-20% of cats! 

A small study was recently published in the Journal of Feline Medicine and Surgery that aimed to identify the clinical occurrence of hypertensive encephalopathy in cats. In this study, 31 of 56 cats were diagnosed with neurologic signs associated with hypertension. Retinal lesion were identified in 28 of the 30 cats that under went fundoscopy. 

Cats with neurologic signs presented most often with proprioceptive ataxia, some with vestibular ataxia. Additional signs included hiding, disorientation, sleeping in unusual locations, increased and inappropriate vocalization, and increased appetite. Three of the 31 cats had seizures. Neuroanatomic lesion localization was predominantly prosencephalon, second most commonly vestibular signs and lastly spinal cord signs. Many cats had multifocal neurologic signs. 

Treatment and Outcome

Amlodipine was used in 22/31 cats. Telmisartan was used in 4/31 cats. The remaining cats received combination therapy. Follow-up was available for 25 of 31 cats. Fifteen cats had complete recovery after starting antihypertensive medications including one cat with severe seizures. Partial improvement was noted in 8/25 cats with residual ataxia or seizures manifesting most commonly. No initial response to treatment was noted in 2 cats with subsequent euthanasia within 1 week of treatment initiation. 

Key points:

• Feline hypertension is common (they enrolled 56 cats in less than 2 years!)

• Neurologic and behavioral signs occurred in more than 1/2 of the cats in this study but clients weren't aware of the significance!

• Treatment with antihypertensive medication can result in improvement

• Routine monitoring for hypertension is recommended in at risk cats, especially those with neurologic signs!

Reference: https://doi.org/10.1177/1098612X231153357

Thanks for reading! Have a terrific week; I look forward to working with you soon. Remember to sign up for the July CE if you are planning on attending because space is limited!

Bile Acid Testing For Dogs with Seizures

Case scenario: You are presented with a 2 year old Labrador retriever with a history of 3 seizures in the past 1 month. The seizures are consistent with generalized seizures and last less than 1 minute. Further questioning of the client reveals the dog to have normal activity, appetite, and mobility at home between seizures. You perform a neurologic examination (yay!) and no abnormalities are found. 

What is the likelihood of idiopathic epilepsy in this dog?

According to the International Veterinary Epilepsy Task Force, a diagnosis of idiopathic epilepsy can be made, at a Tier I level of confidence, if a dog is between the ages of 6 months and 6 years, has had 2 or more seizures, has a normal interictal neurologic examination AND has normal CBC, serum biochemistry and dynamic bile acid testing (that means pre and post feeding testing). We know Labs are commonly diagnosed with idiopathic epilepsy and that a genetic inheritance is known or suspected for most of the breed. So, do we really need to do a bile acid test? 

First, a little background. Minimum data base (MDB) pseudohepatic function tests include glucose, BUN, albumin, ALP and ALT. A pre-prandial bile acid test alone, called a resting bile acid test, is different than a dynamic bile acid test which includes both pre and postprandial samples. 

Do we Reallllly Need to Perform Dynamic Bile Acid Testing?

An article from England recently addressed this question in a publication in the Veterinary Record (DOI: 10.1002/vetr.2585).

Questions asked:
1. If  a dog has a normal MDB, how likely are we to finding an elevated postprandial bile acid test?" Answer: 24 dogs out of 202 dogs

2. How likely is a dog with a normal MDB and a normal pre-prandial bile acid test to have an elevated postprandial bile acid test? Answer: about 9 out of 100 dogs

3. What is the prevalence of a clinically significant hepatopathy in a dog with a normal MDB and normal pre-prandial serum bile acid test (if we don't do a post-prandial bile acid test)? Answer: 1.29%

The authors compared this to the risk of missing a significant brain lesion in a dog less than 6 years of age with a normal neurologic exam in which an MRI is not performed. (About 2.2% of cases would have had a brain lesion missed.) The question always begs, how much of a risk taker are you, or your client?

Based on the information from this study, here is what I propose we do:

• ALWAYS check CBC, serum biochemistry for every dog with a history of 2 or more seizures.

• ALWAYS recommend a pre AND post bile acid test for every dog presenting with a history of 2 or more seizures, even if CBC and serum biochemistry are normal. When making this recommendation I suggest that we make clients aware of the less than 2% chance that their dog could have a significant hepatopathy that will be undiagnosed if we do not perform these tests. This hepatopathy may be the reason for their seizures or, and perhaps more importantly, it could affect how they metabolize many of the anticonvulsants that we use. I'm looking at you phenobarbital, zonisamide and diazepam! Poor hepatic function could result in poor metabolism of these anticonvulsant drugs even if the hepatopathy isn't severe enough to be the seizure etiology. 

• ALWAYS perform a neurologic examination to document any abnormalities before starting any medications for seizures. (Okay, so this wasn't part of the study but I still think this is a must!)

Thanks for reading! This was a very informative article so check it out for more detail! 

Have a seizure patient that you need a little backup for? Seizure management is my passion so I'd love to help! Email me or hop on my website to schedule a consult. Have a great week!

Bacterial Meningitis in Dogs

Bacterial meningitis or meningoencephalitis is rare in dogs. A recent study evaluated clinical presentation, treatment and outcome in a group of 24 dogs. It is good to note that these 24 dogs were accrued over 10 years from 5 different referral clinics, reflecting the rare nature of this disease. That said, when I suggest meningitis as a differential diagnoses to clients, many of them assume I mean bacterial meningitis. Immune mediated meningitis makes up about 98% of the cases of dog meningitis we see however, infectious meningitis is still possible! I thought we could review bacterial meningitis in light of this recent publication from the UK. 

What is a typical presentation for bacterial meningitis?

For humans, pyrexia, cervical hyperpathia and altered mentation are the three signs often attributed to bacterial meningitis. About 20-45% of people present with all three signs and most of these are older people. In the recent study (https://doi.org/10.1111/jvim.16605), only 2 dogs (8%) had all 3 signs, 4 dogs (17%) had only 2 signs and 12 dogs (50%) had 1 of these signs. The remaining 6 dogs did not have any of those three signs. Almost 1/2 of the dogs presented with vestibular signs and were diagnosed with bacterial meningitis secondary to otitis media/interna. The conclusion of the authors was that an absence of these signs should not exclude a diagnosis of bacterial meningitis. I would add to this that the presence of those three signs is not pathognomonic for bacterial meningitis either!

How is it diagnosed?

Positive CSF culture, observation of intracellular bacteria on CSF analysis or (in rare cases) positive outcome with antibiotic treatment only were the diagnostic criteria for the aforementioned study. Less than 40% of CSF cultures were positive! Culturing CSF has always been incredibly low yield which is why we don't do it very often in veterinary medicine. Urine and blood cultures were all negative in this study. Most often, intracellular bacteria were noted on CSF evaluation. A combination of MRI or CT and cerebrospinal fluid analysis resulted in the diagnoses for most of the patients in this report. The few dogs were diagnosed with bacterial meningitis without intracellular bacteria, and without a positive culture, but with a positive response to antibiotics. This last group *probably* had bacterial meningitis but I feel a little unsure including it a published study. 

Treatment and Outcome

The median duration of antibiotic therapy was 8 weeks but there as no real standardized treatment. In humans, treatment times range from 1-4 weeks. The antibiotic chosen seemed clinician dependent and ranged from amoxicillin to cephalosporines, second generation fluroquinolones. About 75% of dogs received a glucocorticoid before referral or at the referral center. Glucocorticoid use is controversial but has been shown to be useful in human medicine to reduce inflammation in the acute stage of disease. The current study was too small to make any conclusions about the utility of glucocorticoid steroids in bacterial meningitis with dogs. Outcome was favorable in the dogs in this study. Survival data for longer than 21 days suggested that about 1/2 of the patients had residual deficits, the remainder did not. The majority (19 of 24) survived to 21 days. 

Although rare, bacterial meningitis or meningoencephalitis is a complicated and potentially life-threatening CNS infection that is worth keeping on our radar. Although immune mediated forms are much more common, we always check for infectious meningitis before instituting immunosuppressive doses of steroids whenever possible for this reason!

Have a great week! I'm back to my usual schedule so if you cannot find a suitable time spot please email me; I'm sure we can work something out!

Early detection of Pug Encephalitis

Pug encephalitis, termed necrotizing meningoencephalitis (NME), is a common cause of CNS inflammation in Pug, Maltese, Chihuahua, Shih Tzu and other small breed dogs. The typical presentation is a dog less than 4 years old with acute, progressive, multifocal CNS signs. (However, meningoencephalitis is the great pretender so it may present in ANY age, breed, sex, and with neurologic examination findings!) Many Pugs are reported to be resistant to immune suppression, however this is not a global truth. On histopathology, areas of necrosis are identified, along with infiltration of inflammatory cells which leads to the term necrotizing meningoencephalitis. Antemortem, a diagnosis cannot be rendered. MRI and CSF changes would lead a practitioner to a diagnosis of meningoencephalitis but without histopathology (biopsy or necropsy) the dog would be diagnosed with meningoencephalitis of unknown etiology (MUE). MUE includes the necrotizing meningoencephalitis and granulomatous meningoencpehalitis thus it is not a histopathologic diagnosis but a clinical one.

What if we could detect NME earlier?

Researchers recently published a study with this question in mind. They evaluated 36 pug dogs that were deemed clinical normally by their owners. Genetic studies were performed; 5 homozygous/high risk, 19 heterozygous/medium risk and 12 low genetic risk (previously published data about genetic link) dogs were included. They then performed 2, sequential neurologic examinations on these dogs at least 4-6 weeks apart. Dogs that were considered repeatably abnormal subsequently underwent MRI (spine, brain, or both) and had a CSF analysis performed.

Results of the study

Dogs considered low risk had 0 repeatable abnormalities on neurologic examination. Eight of the 36 "at risk" pugs had repeatable abnormalities. Abnormalities included back pain, menace deficits, ataxia and paw replacement deficits (1 or more). The only statistically significant finding was multifocal spinal pain. The 8 dogs underwent imaging and mild brain abnormalities were noted in all dogs with variable severity. CSF changes were noted in 3 of the 8 dogs.

What is the actionable result of this study?

The take away here is that the MRI was more sensitive to detecting "pre clinical" NME than CSF analysis. Is this actually "pre clinical" if the dogs had repeatable neurologic examination abnormalities? I argue perhaps not, perhaps they were "undetected" by clients rather than preclinical. That said, we don't subject dogs to annual neurologic exams without reason so perhaps this is a reasonable way to conduct the study. (Maybe we should??) I always ask myself: what I would do with the information gained when I suggest a test or procedure? In this case, would I treat this dog with "pre clinical" MRI changes or would we wait to see if this develops into progressive disease? I don't know the answer to this question and they didn't pursue treatment in this study so I don't have an objective answer for you. For me, these types of studies will help us help dogs considered genetic "at risk" for NME. Perhaps we identify treatment earlier? Perhaps we find out that there is a specific environmental trigger? Perhaps you learned that there is a genetic "risk" for pugs. Have a pug patient or pet that you think should be genetic tested? Here is the link: http://www.vgl.ucdavis.edu/services/dog.php

The big question is - at risk does NOT equate to disease - so what do we do with the information??

Thanks for reading today. I really enjoyed reading this study and hope you enjoyed my summary.

Have a great week and keep those consults rolling. My kids will be in and out of different camps this summer so my schedule will be changing week-by-week. As always, please reach out if you cannot find a suitable time for your patient using the online scheduler and I will do my best to find timely spot!

How to handle a jerk

Have you evaluated an elderly patient with a history of sudden, unprovoked jerk movements lasting several seconds and not been sure what to make of it? It's easy to disregard this information because it doesn't fit into one category but perhaps, we shouldn't.

Myoclonic "jerks" can occur as a part of an epileptic syndrome (myoclonic epilepsy) or as a separate movement disorder. As a movement disorder, they may arise from neuromuscular, spinal, cortical or subcortical origin and therefore may have many different etiology. A report in Cavalier King Charles Spaniels came out recently (https://doi.org/10.1111/jvim.16404) which detailed myoclonic jerks in older CKCS. This study was not conclusive about the origin of the jerk, but suggested a cortical or subcortical origin. Several of the dogs in this group had idiopathic epilepsy, diagnosed with MRI/CSF/blood work prior to the onset of the myoclonic jerk so it is possible this is simply a manifestation of their epileptic syndrome. However, several of the dogs were on treatment with primary anticonvulsant drugs (imepitoin and phenobarbital) and the seizures improved but the myoclonic jerk worsened! This suggests a more likely non-epileptic origin. This study was SMALL so it is much too early to draw conclusions about the cause but it does provoke thought.

Here is what I took away:

1. Older adult or geriatric onset myoclonic jerks may be seizure, or non-seizure in origin
2. Phenobarbital (and imepitoin) didn't help
3. Levetiracetam helped in 3 or 6 cases. This could mean it is epileptic or non-epileptic in origin, remember!
4. If non-epileptic in origin, myoclonic jerks do not warrant treatment as they are unlikely to result in progressive neurologic disease (but knowing if they are non-epileptic is difficult)
5. Myoclonic jerks are seen as rapid movements of the face, head or thoracic limbs that are several seconds in duration and do not have a pre or post ictal period associated with the signs. Not sure what I'm talking about? Follow the link to the article and scroll to the supplementary material. There are two videos attached to help you visualize what is being noted.

So what do I do?
1. If the neurologic examination is ABnormal - suggest diagnostic imaging of the brain or spinal cord to determine if pathology is present to account for the jerk motion.
2. If the neurologic examination is normal, consider non-epileptic jerks and either start levetiracetam or monitor if infrequent.

Thanks for reading and have a great week! Stay cool out there and watch out for jerks!

Strokes in Dogs

Strokes are an increasingly common cause of seizures and other intracranial signs in dogs (and cats). Why is the diagnosis becoming more common? My theory is that we are simply performing more MRIs, and therefore making the diagnosis more readily, but it is possible that increasing comorbidities or breed related changes may contribute to the increase in diagnosis.

What is a Stroke?
Stroke, or cerebrovascular disease (CVD) occurs when normal brain fuction is disrupted due to hemorrhage or infarction. CVD is typically due to occlusion of an/multiple intracranial vessels however hemorrhagic strokes can occur in rare cases. Around 50% of dogs will have an underlying predisposing facture such as hyperadrenocorticism, hypothyroidism, protein loosing nephropathy, heartworm disease, heart disease (less common as a cause!) or other "hypercoagulable" diseases. The other 50% do not have any identified predisposing factors and are therefore considered to have had an idiopathic vascular event.

Clinical presentation
Acute onset, with progression not typically noted after 24 hours (but it can in rare cases)
Common in older dogs, less common/rare in younger dogs
Gait changes (hypermetria, ataxia) and seizures were the two most common presenting complaints leading to a diagnosis of CVD

Diagnosis
The best diagnostic tool for CVD is MRI. Indication of vascular occlusion can be seen immediately but tell-tale signs may resolve if imaging is performed too long after the onset of the clinical signs.

Treatment
Supportive treatment is often the only treatment needed. Supportive treatment may include anticonvulsant drugs, intensive nursing care if non ambulatory, or rehabilitation if gait abnormalities are identified. A neurology consult may help guide treatment for you and the client.

Outcome
The majority of dogs will improve following CVD but time to improvement and degree of improvement is variable, and based on severity of neurologic impairment, and MRI findings. Recurrence can occur, but is less common. We previously though it was rare, but in one study in Japan (see below) 11 of 50 cases available for follow-up had clinical signs of recurrence of disease after a diagnosis of CVD. Recurrence does not mean seizures - remember they can develop a seizure disorder secondary to a CVD but that does not suggest progression!

Other Cool Facts
The Japanese study referenced below noted August and December as months with significantly higher stroke diagnoses, compared to all other months, and October as the lowest month. Interesting!

Thanks for reading! Have a great week and keep those consults rolling! I will be speaking at the Michigan Vet Med meeting in Lansing and at the Chicago Vet conference the week of May 9th so no live consults will be available that week. However, I will be reachable by email or telephone if you need me. I look forward to working with you when I return!

Reference: Ozawa T, Miura N, Hasegawa H, et al. Characteristics of and outcome of suspected cerebrovascular disease in dogs: 66 cases. JSAP (2022)' 63, 45-51.

How reliable is the neurologic exam for patients with vestibular disease?

We (neurologists) like to think that the neurologic examination is the ultimate-be-all-end-all tool. But in dark corners, we talk about how incredibly hard it can be to do on patients with vestibular disease.
First, there are three parts that we need to consider for the lesion localization, correct?
1) Brainstem
2) Cerebellum
3) Peripheral CN 8
My rule of thumb is this: If the pet has ipsilateral hemiparesis/monoparesis, ipsilateral paw replacement deficits or decreased mentation (obtunded, stupor, coma) it is a brainstem lesion. If the pet has hypermetria, or intention tremors along with the vestibular signs, it is cerebellar in origin. Finally, in absence of those findings the lesion is localized peripherally.

An article out of Europe in 2019, dispelled our fears of the neurologic examination failing us and (thankfully) helped us sleep better at night when it was published that the neurologic examination correctly predicted if the vestibular signs were central (brainstem or cerebellum) or peripheral (cranial nerve 8) over 90% of the time.

Interestingly, central disease was more common in this study and, it was localized correctly MORE often than peripheral disease was localized correctly. In other words, dogs with central disease were more likely to be localized on the exam as having central disease compared to dogs with peripheral disease which were occasionally incorrectly localized with central disease.

A few more good reminders:

• Nystagmus are not a localizing sign! (E.g. 8 dogs with peripheral and 5 dogs with central disease had horizontal nystagmus.)

• The onset of disease does not predict it's lesion localization. (E.g. Acute and chronic onset of signs were not statistically different between the central and the peripheral groups.)

• They had a lot of French Bulldogs in the study! Huh..I'm not sure I've noticed an over representation of French Bulldogs in my clinical work. It's good to learn something new everyday.

So, what does that mean for us?

It means if you do a thorough neurologic exam, you'll be correct about 90% of the time when you guide a client towards an MRI and spinal tap (for central disease) or treat for idiopathic or otitis (for peripheral disease). If you're unsure, err on the side of it being a central lesion and recommend a full work up. (Or contact me for a consult!) Oh, and 68% of dogs diagnosed with peripheral vestibular were idiopathic! Idiopathic disease means we have a lot more to learn...so let's get back to it!

(Bongartz U, et al. Vestibular Disease in dogs: association between neurological examination, MRI lesion localization and outcome. JSAP 2019).

Thanks for reading! This was an oldie, but a goodie and I hope you enjoyed revisiting it along with me. Please reach out if you have any questions. Have a great week

Help! My patient sustained head trauma!

Help! My Patient Sustained Head Trauma!

Traumatic brain injury (TBI) in dogs and cats is a dynamic process. The outcome depends not only on the severity of the primary injury, but also on the resulting secondary effects. Primary injury is defined as injury that occurs at the moment of impact and results in physical disruption of tissues (fracture, etc.).  Secondary injury is defined as the physiologic alterations that occur hours to days after the primary injury. Medical therapy is aimed at affecting secondary injury. Animals with TBI frequently have serious injuries elsewhere and shock, hemorrhage, airway obstruction, pneumothorax, and traumatic cardiac arrhythmias should be detected and treated timely. 
 
Pathophysiology
Following TBI local vascular disruption can cause hemorrhage, which results in deposition of iron, free radical formation and mass effect. The effects on the vascular system contribute to vasogenic edema. Cytotoxic edema is the other type of edema that can occur in head trauma. Cytotoxic edema forms when excessive neurotransmitters are released by surrounding cells, which cause overstimulation of neurotransmitter-dependent channels, causing excessive intracellular accumulation of sodium and calcium. Increased intracellular sodium results in an osmotic draw of water into the cell, causing swelling and possibly apoptosis.

Cerebral Perfusion and the Cushing's Reflex
Cerebral perfusion is the driving force behind cerebral blood flow and cerebral blood flow is reduced in the first 24 hours following traumatic brain injury. Reductions in cerebral blood flow can result in poor delivery of oxygen and metabolic substrates and inadequate removal of waste and CO2. CO2 is a potent vasodilator, therefore excessive local CO2 may result in local (or global if severe enough) vasodilation. Maintaining cerebral perfusion, and therefore cerebral blood flow is critical in the head injured patient. There are several equations that are commonly used in TBI and they include:

CPP = MAP – ICP1
CBF = CPP/CVR

CPP = cerebral perfusion pressureCBF = cerebral blood flowMAP = mean arterial blood pressureCVR = cerebral vascular resistanceICP = intracranial pressure

Animals with TBI may develop focal or global increases in CO2 as cerebral blood flow decreases, which result in vasodilation and therefore causes worsening CBF. Following TBI, the brain’s intrinsic ability to manage cerebral blood flow and perfusion pressure becomes altered. Vasomotor centers in the brain may detect increased CO2 and attempt to vasoconstrict through increase in sympathetic function. Systemic hypertension then occurs, which is noted clinically as an increase in MAP. This increase is detected by baroreceptors and a reflexive bradycardia ensues. Animals with decreased mentation, hypertension and bradycardia are at increased risk of having or eminently developing increased ICP. This triad of abnormalities (bradycardia, hypertension and altered mentation) in a post-traumatic patient is called the Cushing’s reflex. The end result of excessive increased ICP is brain herniation.

Management of the Head Trauma Patient
1) Get oxygen to the brain:  A clear airway must be established, oxygen and CO2 status should be determined. If oxygen supplementation is required, an oxygen cage or mask may be used. Remember to avoid nasal canula as sneezing can increase ICP. Also, oxygen supplementation will correct hypoxemia, but will not prevent hypercarbia in a hypoventilating animal. Tracheal intubation and mechanical ventilation is indicated in animals that are apneic or hypoventilating.
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2) Monitor blood pressure and heart rate: Head-injured patients require maintenance of systemic and cerebral hemodynamics. The two most important goals are preservation of CPP and maintenance of systemic oxygen availability. Ideally mean arterial blood should be constantly monitored in these patients. Hemodynamic goals include a MAP>80-90 mm Hg and <115-120 mm Hg. Fluid restriction is NOT encouraged in the post-traumatic patient because of the risks to systemic health and the minimal benefit to reducing cerebral edema. Colloidal support may improve blood flow (and perfusion) however, the 2007 SAFE study in human TBI demonstrated an increased mortality in patients receiving albumin compared to those receiving saline rehydration. It remains unknown if all colloidal support would have the same outcome.3 
3) Manage Increasing intracranial pressure: Mannitol (1 gm/kg slow IV over 20-30 minutes) has become a cornerstone in the management of increased ICP. There are several proposed mechanisms of action by which mannitol decreases ICP. 1) It expands circulating volume, decreases blood viscosity and therefore increases cerebral blood flow and cerebral oxygen delivery. 2) Reduction of CSF production 3) free radical scavenger   4) Delayed effect:  osmotic action: transfer of extravascular edema fluid (in neurons) into the intravascular space: occurs 15-30 minutes after administration when gradients are established between plasma and cells. The effects of mannitol persist for a variable period ranging from 1 to 3 hours depending on clinical conditions. Mannitol can be administered as repeated boluses, or continuous infusion.  Due to a rebound effect, risk of hypernatremia and hyperosmolarity, mannitol should not be administered more often than 3 times over a 24 hour period. Dangers of repeated dosage are related to effects on blood volume and electrolytes rather than specific toxicity and the patient's blood volume status should be closely observed. Hypertonic saline may also be used instead of mannitol and is considered equivalent by most neurologists for most patients. Hypertonic saline (4 mL/kg of 7.5% or 5.4 mL/kg of 3%) has the added advantage of rapidly restoring volume by causing an osmotic shift from extracellular to intravascular space. Due to the high sodium level, salt toxicity is possible therefore; serum sodium levels should be frequently monitored.  The exception may be patients that are volume depleted; these patients may benefit from hypertonic saline more than mannitol. For a favorable prognosis, a response to medical therapy should be seen within 4 to 6 hours following commencement of treatment. An animal should be assessed every 30 minutes until stabilized.
Glucocorticoids are contraindicated in TBI due to the exacerbation of hyperglycemia.  The majority of available evidence indicate that glucocorticoids do not lower ICP, or improve outcome in severely head-injured patients.

Monitoring of TBI patients
1) respiratory status, pupil size (and PLR) and level of mentation. In a very simplistic sense, inspiration and expiration are initiated in the medulla, and the rate and pattern is driven from the midbrain/pontine centers. Feedback loops, largely responsive to blood levels of CO and oxygen are present in the prosencephalon as well. Damage to specific areas of the brain will result in specific respiratory patterns.
2) Monitoring pupil size can help with formulating a prognosis (see below) and aid in initial lesion localization.  Sympathetic function to the eye originates in the thalamus, descends through all parts of the brainstem and exits the spinal cord T1-T3. Damage to this tract will result in an inability to dilate the eye, or miosis. This most often occurs with damage to the thalamus (prosencephalon) or medulla. Parasympathetic innervation to the eye starts in the midbrain and goes to the eye by traveling along with the somatic fibers of cranial nerve 3. Damage to the midbrain would result in an inability to constrict the eye, or a dilated fixed pupil. If both the sympathetic and parasympathetic fibers are damaged the eye will appear fixed and midrange.
3) Monitor mentation changes are described as obtunded, stupor or coma. Obtunded animals have diminished responsiveness to the environment but will respond to tactile, visual or verbal stimuli. Animals with stupor will only respond to firm tactile stimuli (not visual or verbal) and animals in a coma will not respond to sharp tactile stimuli such as pinching with a hemostat. Body posture can also help one lesion localize the problem. Decerebrate rigidity occurs with damage to the descending corticospinal tracts, usually at the level of the midbrain. Animals have increased extensor tone to all limbs and severely decreased mentation, usually coma. This indicates a poor prognosis. Decerebellate posture occurs with damage to the cerebellar peduncles and typically has a fair to good prognosis. Patients demonstrate forelimb extension, variable pelvic limb positioning and normal mental awareness.
 
Prognosis
Both the modified Glasgow coma scale (MGCS) and animal trauma triage (ATT) score have been used to provide estimated, objective assessments for prognostication in animals. For the MGCS, motor activity, brainstem function and level of consciousness are scored  and then compared to a graph to determine the relative survival probability.5  For the MGCS, the LOWER the number, the LOWER the probability of survival. Remember to perform 2-3 GCS before considering the number reliable if the animal is in the immediate post-traumatic period. This scale is useful for adjusting the prognosis on a daily basis, as the patient progresses through treatment.
Unlike the MGCS, the animal trauma triage score accounts for more than just intracranial trauma. Scores are summed for each of the following six categories: perfusion, cardiac, respiratory, eye/muscle/integument, skeletal and neurological. Scores are 0-3 for each category resulting in a maximum score of 18. The LOWER the number the HIGHER the probability of survival. 6 For each increase in 1 point, there is a 2-2.6x decrease in survival.7 One recent study compared the two scoring systems for animals with head trauma and identified the ATT as a more predictive and reliable scoring system.7
 
References:
1.          Kuo KW, Bacek LM, Taylor AR. Head Trauma. Vet Clin NA Small Anim Pract. 2018;48(1):111-128.
2.          Van Beek J, Mushkudiani N, Steyerber E, et al. Prognostic value of admission laboratory parameters in traumatic brain injury: Results from the IMPACT study. J Neurotrauma. 2007;24(2):315-328.
3.          SAFE study I, Australian and New Zealand Intensive Care Society Clinical Trials G, Australian Red Cross Blood S, George Institute for International H, Myburg J, Cooper D. Saline or albumin for fluid resuscitation in patients with traumatic brain injury. N Engl J Med. 2007;357(9):874-884.
4.          Hayes GM. Severe seizures associated with traumatic brain injury managed by controlled hypothermia, pharmacologic coma, and mechanical ventilation in a dog: Case report. J Vet Emerg Crit Care. 2009;19(6):629-634.
5.          Platt SR, Radaelli ST, McDonnell JJ. The prognostic value of the modified Glasgow Coma scale in head trauma in dogs. J Vet Intern Med. 2001;15(6):581-584.
6.          Rockar RA, Drobatz KS, Shofer FS. Development of a scoring system for the veterinary trauma patient. J Vet Emerg Crit Care. 1994;4(2):77-83.
7.          Ash K, Hayes GM, Goggs R, Sumner JP. Performance evaluation and validation of the animal trauma triage score and modified Glasgow Coma Scale with suggested category adjustment in dogs: A VetCOT registry study. J Vet Emerg Crit Care. 2018;28(3):192-200.


That's it for now! I'm maintaining curbside servcie for the summer and am starting to widen my travel radius again. Please reach out if I can assit with a case. Stay safe, stay healthy!