head tilt vs head turn in dogs? How do you use this informatin to localize?
How do MRI lesions affect survival for MUE?
A study was published this week that looked at the survival times between dogs with and dogs without MRI lesions and diagnosed with meningoencephalomyelitis of unknown etiology (MUE). MUE is diagnosed if a dog has evidence of CNS inflammation (meningitis, encephalitis, myelitis or a combination of these) without evidence of infectious etiology. Signs can be focal or multifocal, and age is irrelevant. To make this diagnosis an MRI, CSF tap, and infectious disease testing are performed. There is a subset of dogs that are diagnosed with immune mediated CNS disease that do not show evidence of disease on MRI but have all of the other markers of MUE. The purpose of this paper was to determine if there is a difference in survival between the two groups of dogs.
Results
A total of 73 dogs with MUE were included in the study. This included 19 dogs with a normal MRI and 54 with an abnormal MRI. The survival time was >107 months in both groups with a significantly longer survival in the normal MRI group. Neither group reached median survival in Kaplan-Meier survival, however. Death was secondary to MUE in 1/19 dogs with a normal MRI, and 18/54 in dogs with an abnormal MRI.
Below is the breakdown comparison between the two groups:
Remission – 68% of the normal MRI group; 53% of the abnormal MRI group.
Death within 3 months due to disease – 5% in the normal MRI group and 13% in the abnormal MRI group.
No difference was found between dog groups regarding remission, disease-free interval, or relapse while on prednisone. The two groups received similar treatment protocol, for which corticosteroids were included in all dogs and a variation of additional immunosuppression. The total nucleated cell count (TNCC) was higher in the dogs with the abnormal MRI however this did not correlate with higher rates of death after multivariate analysis. The only significant factor associated with death was the presence of an abnormal MRI.
Why don’t they have lesions on MRI?
Perhaps we’re catching these cases early in the course of disease. This would stand to reason why they might have a lower death rate than those with more progressive disease at the time of diagnosis. Another option is that this is a different form of inflammatory brain disease. MUE is a “catch all” for inflammatory brain disease that isn’t infectious, or a specific form such as SRMA or EME. It likely includes all of the previously diagnosed cases of GME and NME.
Take away: If you have a dog with spinal pain, seizures, vestibular signs or multifocal CNS signs remember MUE! This disease can cause all of those signs, and a collection of other signs, in dogs. Early detection may = improved outcomes. So, if your patient is showing neurologic signs, please reach out to get a consult ASAP and to proceed with additional testing when able. We might just save their life!
Thanks for reading! I hope you are scratching out the very best that summer has to offer. I look forward to working with you soon!
Reference: Survival in dogs with meningoencephalomyelitis of unknown etiology with and without lesions detected by magnetic resonance imaging. Ostrager A, Bently, TR, Lewis MJ, Moore GE.
Neurodisability Score for MUO
As discussed last week, a neurodisability score (NDS) has been proposed for use in dogs with meningitis of unknown origin (MUO). The goal is to help grade the clinical signs more objectively and, hopefully, prognosticate more accurately. The score was developed by Drs. Goncalves et al (https://doi.org/10.1111/jvim.16717) from the UK and published in 2023.
A retrospective evaluation of medical records was performed to identify common clinical signs at presentation. Subsequently these signs were grouped in to the following categories for prospective use: seizure activity, ambulatory status, posture and cerebral, cerebellar, brainstem and visual signs. For the prospective part, the score was tested on 31 dogs diagnosed with MUO. Table 2 of the published article has an outline of the scoring system which I would suggest you look at if you have time. As an example, under the “ambulatory status” section the options are “normal, mild paresis or ataxia but ambulatory without falling, moderate/severe paresis or ataxia with frequent falling, and nonambulatory”. Each of these options is given a numeric score from 0 (least severe) to 3 (most severe). As the categories are worked through, points will be accrued based on their neurologic exam. The maximal score is 21, indicating he most severe disease. According to the article, the mean score at presentation was 8 +/- 2.85 points. All of the things that you imagine would affect this score such as concurrent disease, treatment prior to referral, and evaluator skill must be considered here (which the authors did consider, for the most part). In the end, they found a significant difference in dogs that survived to discharge (median 8; range 3-14) and those that did not (median 12.3; range 8-13). You can see as well as I can that there is marked overlap between the ranges which makes it difficult in a clinical patient to draw conclusions. Furthermore, the study did not evaluate validity (did the test measure what it was supposed to be measuring) and did not find an association at a specific cut-off value related to long-term outcome. The study presented in last weeks TidBit Tuesday suggested a cut off value of 7 would be used to predict death by 6 months for dogs with MUO. I’m ecstatic that this work is being done but caution you to use it with care. Euthanizing a pet simply based on this score feels inappropriate at this time. Predicting a poorer possible outcome at 6 months and relaying this information to a client would be an appropriate use of the NDS. It IS encouraging that we may have a universally available tool for ALL VETS (i.e. not a specialty tool like an MRI, or a neurofilament in CSF) that we can use to talk about MUO in objective terms. As with most of the TidBit Tuesdays there will be much more to come on this topic over time so stay tuned!
Thanks for reading! Changes to my schedule are once again upon us as the summer sets in. My schedule varies WEEKLY so please reach out if you have a case that needs to be seen but cannot find a suitable time on the schedule; I may have more flexibility than what is listed, so please ask. I will be closed at the end of June for a few days for a family wedding, and mid-July for the Dane County Fair but otherwise anticipate high availability for you this summer. Enjoy the beautiful spring weather and the delicious smells of blooming things this week!
The Prognosis Meningoencephalitis of Unknown Origin
Meningoencephalitis of unknown origin (MUO) is a frequent diagnosis for dogs with multifocal neurologic signs. The name should tip you off that we’re still figuring out this interesting disease amd do not know the underlying cause yet. It is thought to be immune mediated, and therefore treatment often includes an immunosuppressive dose of steroids +/- an additional immunosuppressive such as cytarabine, azathioprine or cyclosporine. Despite decades of awareness of this disease we are still working out the prognostic indicators. Back in my academic days, a resident of mine and I tried to sort out this question by evaluating brain MRI results, with little success. A recent study took another crack at the elusive prognostic indicators and published their findings in JVIM (Goncalves R, et al. JVIM 2024).
Materials and Methods
447 dogs were included in this retrospective study from 2 institutions. Did you see that giant number of included cases?? Go vet med, go! Anyhoo, the authors included dogs with signs of inflammation (brain MRI, spinal tap) and because it was a retrospective study, there were a number of different treatment protocols included. Perhaps this creates too much variability to carefully evaluate outcome or prognosis. I might argue that there is no other way to accrue a large number of cases of MUO. A neuro disability score (NDS) was assigned to these patients (score developed by the author and several others and published in 2023). Survival was reported.
Results
I’m going to list some of the key results below but if you wish to learn more about the results, please refer to the article. It is well written and comprehensive.
Median age at presentation was 48 months
The majority of breeds represented were small breeds, but a few Labs, spaniels, and larger dogs were also included.
The season of diagnosis was equal across all 4 seasons
Common presenting complaints were proprioceptive deficits (77%), ataxia (65%), obtunded mentation (62%), seizures (32%).
The most common neuroanatomic lesion localization was multifocal (43%), followed by forebrain (29%)
Median follow-up time was 11 months. 82% of dogs survived to discharge and 63% were alive at 6 months.
A significant difference in survival was noted for dogs WITH a NDS compared to those without and a score of greater than 7 resulted in a sensitivity of 61% and specificity of 67% for predicting death at 6 months after diagnosis.
Relapse occurred in 50% of dogs that survived to discharge
Of those that relapsed, incomplete resolution of neurologic disease during the 6 month follow-up period, a higher NDS and neurologic signs >7 days duration before intervention were statistically associated with relapse.
What should we do with this information?
The take home message should be that we should perform a NDS on patients with suspected or confirmed MUO to help provide a prognosis AND that a more rapid referral may provide a better long-term outcome.
Stay tuned next week for a review of the NDS! Thanks for reading and I Hope you have a great rest of your week!
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 are 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. A persistent seizure disorder is possible following a CVA. Repeated seizures, without the development of other neurologic signs, could suggest a seizure disorder and NOT progression or regression of disease.
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! With the onset of winter weather, mobile neurology consultations may become challenging at times. Remember a video consult may suit your needs if I cannot be on site due to inclimate weather! Stay safe and warm out there this week, folks!
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.
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!
Case Based Practice
Lesion localization is one of those things that can be lost, if not practiced. This week, we’re going to work out those muscles.
Maria, is a 13 year old FS Lab
History: Presented to me with a 24 hour history of acute onset difficulty walking.
Neurologic examination:
Mentation: BAR
Cranial nerves: right head tilt, rotary nystagmus, remainder normal.
Gait: Moderate vestibular ataxia, falling right. No hypermetria or intention tremors noted.
Postural reactions: absent right thoracic and right pelvic limbs, normal other limbs
Spinal reflexes: Normal all limbs, normal c. trunci and perineal
Palpation: non painful, normal cervical ROM
You know what you've got to do now, right?
What is the Neuroanatomic Lesion Localization?
There are several ways to go through lesion localization.
OPTION 1:
I like to make lists. Start by listing all of the abnormalities and ALL possible locations that could result in an abnormal finding. For example:
1) Right head tilt - peripheral CN 8 (right), medulla (right), cerebellum (right or left)
2) Rotary nystagmus - same as above
3) Vestibular ataxia - same as above
4) Reduced paw replacement right side - right C6-T2, right C-C5, right medulla, right pons, right or left midbrain, left prosencephalon.
Now, we start to clump things. Well, for starters any animal with cerebellar disease is expected to have hypermetria and/or intention tremors and Maria did not. We can cross out cerebellar disease. What else? What is the one spot where all of the signs can be explained? That's right - medulla on the right! Voila, lesion localization.
OPTION 2:
The other way to work through this is to identify the cranial nerve affected on the exam (in this case, cranial nerve 8), identify the brainstem segment associated with this cranial nerve (in this case, medulla) and then ask yourself if you can identify if she has a) paw replacement deficits b) hemiparesis and/or c) mentation changes. . If not, it is peripheral and if so, it is brainstem.
Differential Diagnoses
Brain stem vestibular disease in an elderly dog without an important prior medical history would suggest the following differential diagnoses:
Degenerative: none
Anomalous: none
Metabolic: Hypothyroidism
Neoplastic/nutritional: Neoplasia of the brainstem
Infectious/inflammatory/idiopathic: meningoencephalitis (infectious or inflammatory)
Trauma: no supportive history
Vascular: Cerebrovascular accident (stroke)
Final diagnosis: cerebrovascular accident (stroke).
Please reach out if you have a case that is troubling you, a client that needs reassurance that you're doing all you can, or simply have a question. I hope you have a great week!
Rabies: It's Still Out There
Last week, the CDC announced the death of a 7 year old Texas boy from Rabies virus infection. I was saddened for his family, and thought this would be a good time to remind ourselves about this virus. As of October, 14 cases of rabies had been identified in the State of Wisconsin; all 14 were in bats. It's still infecting animals, and therefore a risk to humans, too.
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).
Once neurologic signs are present, progression is rapid, and most animals will be dead within several days. The CDC report says that the boy was bitten by a bat 2 months prior to onset of signs and that he became deceased after 22 days of clinical signs.
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, or wild, 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 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! Rabies virus infection is something I think about daily and is one of the more daunting zoonotic diseases we are faced with. Please reach out if you have any questions!
Please note: If you use my services for live or video neurology consultations, fees are changing January 1, 2023. Please email for an updated fee schedule.
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
Triggers for MUO
Predictive Signs for MUO
Meningoencephalitis of unknown origin (MUO) is a non-infectious, inflammatory brain disease common in dogs. The vast majority of dogs diagnosed with meningoencephalitis have MUE, not infectious meningitis. MUO includes granulomatous meningoencephalitis (GME) and the necrotizing encephalitides (NME,NLE) and is the term used to describe antemortem non-infectious, inflammatory CNS diseases in dogs and cats. Providing owners with a prognosis when diagnosed with MUO is extremely challenging. A recent study evaluated several prognostic factors on the early survival in dogs with MUO. (https://www.sciencedirect.com/science/article/abs/pii/S1090023322000995)
Key Points:
98 dogs with MUO were included. 30/98 died within 30 days of the diagnosis.
Adding cytosar to a glucocorticoid protocol did NOT alter the prognosis.
Obtundation at presentation was the ONLY factor statistically associated with poor prognosis. Dogs had a 6.6x higher odds of death in the first 7 days, 2.1x increased risk in the first 30 days when presenting with obtunded mentation.
What does this mean for your patients?
It means that we still have a long way to go when sorting out what MUO means, and how it affects dogs. It means that a dog with a severely elevated WBC on CSF, or with other abnormalities on neurologic examination do not necessarily have a poorer prognosis. If you are seeing a patient with multifocal CNS neuroanatomic lesion localization, be sure to evaluate the pet's level of mentation. Survival may be reduced if obtundation is present. Refer as soon as possible for a neurology consultation and/or work up, depending on client preferences.
References: Lawn RW, Harcourt-Brown TR. Risk factors for early death or euthanasia within 100 days of diagnosis in dogs with meningoencephalitis of unkonwn origin. Vet J 2022. vol. 287.
Short and sweet this week. This article was too good to pass up, so please excuse the short TidBit Tuesday this week.
Safe fast to those of you observing Yom Kippur, Happy Feast of St. Francis of Assisi day and Happy Cinnamon Roll day to the rest of you! (Yes, that is actually a THING on October 4th.
Neutrophil-Lymphocyte Ratio in MUE
Meningoencephalomyelitis of unknown etiology (MUE) is a challenging antemortem diagnosis. MUE is the term used when we diagnosed inflammatory, non-infectious disease in the CNS. In the old days, we would have called this GME, NME or NLE, depending on the breed. However, those three inflammatory conditions cannot be distinguished on clinical picture, diagnostic testing, or treatment response, alone. Histopathology is needed to determine if a patient has GME, NME, and NLE. Without a brain biopsy, or post mortem sample, we cannot call it GME, NME or NLE. Several years ago, the term MUE started getting tossed around as an antemortem term for inflammatory brain disease, without a biopsy.
To diagnose MUE, a patient must have:
1) a neurologic examination with deficits identified (or a history of seizures) and
2) have a MRI with classical changes and
3) and CSF tap with a lymphocytic or monocytic pleocytosis and/or elevated protein level and
4) negative geographically specific infectious disease panel. If the pet meets these criteria, they can be diagnosed with MUE.
MUE does not show up in routine blood work. Inflammatory leukograms are rare, elevated body temperature is not typically reported and pets are not systemically, clinically ill. However, some immune mediated diseases (such as MS) have garnered attention for a neutrophil to lymphocyte ratio present on routine CBC.
A recent study out of Korea evaluated the ratio of neutrophils to lymphocytes in a standard CBC to see if we could predict a diagnosis of MUE. As it turns out, you can divide the neutrophil count by the lymphocyte count, and get a significantly higher number in dogs with MUE than healthy dogs. Furthermore, the ratio was significantly higher than dogs with idiopathic epilepsy but NOT different than dogs with brain tumors. The neutrophil-lymphocyte ratio was higher in dogs with MUE than all other forebrain diseases (hydrocephalus, idiopathic epilepsy, and brain tumors) but not always significantly so.
What does this mean for us?
Unfortunately, nothing...yet. This is an interesting concept and a step towards a much needed tool for diagnosing MUE without invasive diagnostic testing. Performing a CBC, and calculating the ratio, is both simple and readily available in most (all?) veterinary practices today. However, if the ratio is high, it does not mean the pet has MUE. It may support a diagnosis of forebrain disease (which you already know from your neuro exam) and may support structural brain disease (i.e. not idiopathic epilepsy). Very importantly - this study did not find a significant difference between dogs with brain tumors and those with MUE. Sadly, brain tumors and MUE are often our top differentials for pets with forebrain disease so this ratio does not (yet) give us another non-invasive tool to differentiate between these two diseases.
I enjoyed reading this study and learning about inflammatory markers for humans with MS (the human counterpart to MUE) and how this neutrophil-lymphocyte ratio could be used in the future for pets. If you'd like to read more, please see the link at the bottom of the page.
Thanks for reading! I hope you have a wonderful week and look forward to working with you soon!
If you haven't heard yet, please note that I am moving my office. Please try to remit any outstanding invoices by August 30th. If you need my new invoicing address please email me, or watch for a note in the mail.
Reference: https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvim.16512
Syncope Vs Seizures
Syncope vs Seizures
Seizures and syncope are both described as a temporary loss of consciousness. Clinical signs of seizures often include collapse, some form of somatic movement, and a display of autonomic activation (e.g. urination, defecation, salivation, pupillary dilation) but these signs can be subtle in some patients. Clinical signs of syncope may also include collapse with occasional loss of bladder or bowel function. However, the pathophysiology, differential diagnoses, diagnostic testing and treatment plans are markedly different therefore differentiation between seizures and syncope is critical! What are my top 5 ways to differentiate between seizures and syncope?
Autonomic signs: Loss of bladder control has been reported with syncope and is a common finding with seizures. Other autonomic changes such as loss of bowel function, salivation, lacrimation and dilation of pupils have not been reported with syncope and are regularly reported with seizure disorders.
Post ictal phase: blindness, disorientation and at times, aggression can be seen for minutes to hours following a seizure. Animals with syncope may appear momentarily disoriented but typically they are back to normal within seconds of a return to consciousness.
Timing of the event – It is more common for seizures to occur when the pet is at rest, and syncope to occur when the pet is in motion or accelerating. We know this doesn't apply 100% of the time but can be a very helpful to ask what the pet was doing immediately before it collapsed.
Evidence of metabolic disease: Evidence of metabolic diseases known to cause seizures such as hypoglycemia, hypocalcemia or hepatic failure concurrently identified in a patient with a history of acute collapsing episodes should lead the clinician to consider a seizure disorder. Without a doubt, patients with metabolic diseases can also have concurrent metabolic derangement however I will use this as a tool when trying to sort between seizures and syncope.
Neurologic examination abnormalities. This one is obvious. If the pet has neurologic abnormalities that localize to the prosencephalon (forebrain) it is reasonable to consider this lesion localization over syncope. You could turn this upside down and say that if the pet has evidence of a cardiac arrhythmia or cardiac disease, syncope may be considered more likely. I have seen several patients that have been unfortunate enough to have BOTH syncope and seizures but, thankfully, that is rare.
I hope this helps you differentiate between seizures and syncope. Let me know if you have any other ways to differentiate between seizures and syncope in your practice.
Thanks for reading and stay cool, my friends! Remember, if you're working with a dog or cat with neurologic disease, I'm an email or telephone call away! Better yet, schedule a consult and we can work through the case side-by-side.
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.
Neospora Meningoencephalitis vs Immune Mediated Meningoencephalitis
Immune mediated meningoencephalitis (aka meningitis of unknown origin: MUO) is very common and is a cause of intracranial disease for many pets. Infectious meningoencephalitis accounts for only about 2% of the cases seen through a referral center and is, therefore, in the minority. Infectious meningitis may be secondary to fungal infection, protozoal (Toxoplasma or Neospora), viral, bacterial or in southern states, some tick borne diseases. Neospora infection is one of the more common causes of infectious meningoencephalitis we see in Wisconsin (probably second only to fungal) and therefore one of the main differential diagnoses for a pet with meningoencephalitis. The current way to diagnose Neospora is via serum titer elevation, evidence of encysted protozoa on biopsy or necropsy, or PCR on serum or CSF. All of these tests take a variable amount of time, depending on the laboratory, so some researchers in the UK came up with another idea. (https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvim.16334)
Scientific Question: Can we differentiate between Protozoal meningoencephalitis and MUO using CK and AST values?
Rational: Protozoa (Toxoplasma and Neospora) are often found in muscle which would result in membrane disruption, thus elevating CK (and subsequently AST). Seizures, a common sign of MUO and protozoal meningoencephalitis, can also elevate CK so the researchers also aimed to evaluate the temporal relationship between seizures and CK elevation.
Methods: This was a retrospective study of 59 dogs diagnosed with MUO and 21 dogs diagnosed with Neospora (no dogs were diagnosed with Toxoplasma in this study).
Results: A significantly higher CK and AST value were identified in dogs with Neospora compared to those with MUO. Using a cutoff value of 458 U/L, there was a sensitivity of 95.24% and specificity of 96.61% for active Neospora meningoencephalitis and using a prevalence of 2.25% for active infection in the UK, there was a negative predictive value of 99%. This suggests that dogs with a CK less than 485 U/L are unlikely to have a diagnosis of Neospora infection associated with their intracranial signs. Twenty of 21 dogs with Neospora had CK higher than 485 U/L, and 2 dogs with MUO had CK > than 485 U/L in this study.
Things to remember: CK has a short half-life (22 hours) so if you test, do so within the acute phase of disease. CK and AST are not muscle specific and can be found in myocardium, intestine and AST in the liver also.
What do you do with this information? If you have a dog with suspected meningoencephalitis, consider running a CK and AST on initial blood work. If it is greater than 485 U/L, a Neospora titer should be performed.
Have a great week and thanks for reading!
Note about the holidays: I will be available for emergency cases on December 24, and 25th.
New Years Eve and Day, I will be spending time with my family building a colossal gingerbread house and stables. If I'm not baking, cutting and cooling gingerbread I will be making sticky frosting glue and won't be available for phone calls, texts or email. Thank you for your understanding!
Paroxysmal Movement Disorders
Welcome to another "what-if" TidBit Tuesday! Here we go...
It's Wednesday morning and on your schedule is a 6 month old MC Cavalier King Charles Spaniel to see you for a complaint of "seizures". Upon examination, you find the pet to be normal both physically and neurologically. The client proceeds to describe the events that they've noticed as follows:
"When she goes to jump up on me to greet me she will sometimes fall into a praying position with all four legs stiff. It lasts 2-3 minutes and then she gradually relaxes and is able to walk normally."
Upon further questioning you discover that the dog appears mentally appropriate without signs of drooling, urinating, defecating or vomiting before or after the event. The client provides you a video of the event and at the conclusion, the dog resumes wiggling and excited behavior without obvious change in mentation. Hmmm....no preictal phase, no postictal phase and a relatively long ictal phase. Maybe it isn't an ictus at all???
Hopefully by now you're starting to think this may not be a seizure at all, but in fact one of those "movement disorders" you've been hearing about. What are they, and what can we do?
Movement disorders are a large group of diseases that are non-epileptic changes in muscle tone that happen episodically. They can be triggered by environment, or not. The most common classification that we see in veterinary medicine is a paroxysmal dyskinesia (PD), with or without dystonia. (I'm sorry...say what?? Okay, sorry. Paroxysmal = sudden violent or periodic event; dyskinesia = involuntary, erratic movements of muscles, usually face or limbs; dystonia = sudden muscle contracture, usually of opposing muscle groups which results in a writhing or twisting movement.) There are breed-specific PD which can be found here (https://www.frontiersin.org/files/Articles/163467/fvets-02-00065-HTML/image_m/fvets-02-00065-t005.jpg). Many of these are known to be inherited and some form of genetic mutation has been identified but in some cases we aren't clear on the cause. In humans there are inherited and acquired causes and entire books written about the different forms of movement disorders and their appearance. We don't have that...yet.
Pathophysiology
What happens to cause this, if it isn't a seizure? That is a complex question that I will try to answer simply. Most movement disorders originate from the brain in an area of the basal nuclei. This is where one of the most famous movement disorders, Parkinson's disease, originates from. Pathophysiology is largely unknown for animal movement disorders but there is definitely something going on in the basal ganglia. Diagnostic testing including brain MRI/CSF and at times muscle/nerve biopsies are recommended to pursue an acquired cause. These tests are often negative because inherited causes are more common.
Treatment
Effecting the basal ganglia through the use of benzodiazepine drugs (clonazepam 0.5 mg/kg) or even acetazolamide has shown some improvement. Some dyskinesia respond favorably to zonisamide and potassium bromide as well which further complicates our ability to decide cage-side if this is a seizure disorder, or not. An EEG is valuable here to identify the lack of brain changes consistent with seizures. However interpretation and acquisition of an EEG is challenging making this less available and useful for veterinary patients.
Sometimes it is plain ol' not clear if this is a seizure disorder or a movement disorder and we must do a trial and error with medications. In either case, breeding pets with known or suspected movement disorder OR epilepsy is discouraged due to the likelihood of inheritance.
Do you have a case in which you suspect a movement disorder? Let me know if you want to work through the case together! (Group frustration is much more tolerable than beating your head against the wall - metaphorically speaking - alone!).
Thanks for reading and have a great week! Stay safe, stay well and let me know how I can help you.
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
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!
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!
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!