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

Trace Minerals and Canine Epilepsy

Trace elements are the micronutrients found throughout live animals that are essential for organ function and brain health. They keep mitochondria running smoothly, improve neurotransmission and aid with enzyme function. Deficiency or excess has been linked to multiple neurologic diseases including neurodegenerative diseases, behavior diseases and inflammation in humans and animal species. A recent study evaluated the levels of several trace elements in hair samples of dogs with epilepsy and compared them to dogs without seizures.
 

What Trace Elements were Abnormal?

In this study, by Rosendahl et al, there were 10 epileptic dogs without any treatment, 53 epileptic dogs currently undergoing treatment for epilepsy, and 42 control dogs (no seizure history).

• Phosphorus: lower in epileptic dogs

• Copper: Higher in epileptic dogs

• Zinc: higher in epileptic dogs

• Copper/zinc ratio: higher in epileptic dogs. Specifically, higher in dogs treated with phenobarbital, in one previous study. Studies have shown that copper homeostasis is an important preventative for some neurodegenerative diseases. More work needs to be done in veterinary species to determine if this holds true for our patients, too.

• Selenium: higher in epileptic dogs

• Arsenic: higher in epileptic dogs but also much higher in dogs receiving potassium bromide!

Some of these findings were significant, some were significant only when comparing control dogs with either treated, or untreated dogs, and others were significant for both subgroups of epileptic dogs.

This study is likely to be a stepping stone for either this group, or others, studying trace minerals and their relationship to seizures. It was important work to identify differences, but the clinical significance remains unknown. Treatment, or correction of these deficits or elevations of trace minerals has not been evaluated in epileptic dogs. Stay tuned!
 

Thanks for reading! I hope you have a great week and enjoy what I hope is our final push out of winter, into spring, weather.

 
Reference: https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.16698?campaign=wolearlyview

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!

Unilateral Masticatory Muscle Atrophy

It's a Wednesday morning and you see on your schedule a 7 year old dog with unilateral temporalis and/or masseter muscle atrophy. What parts of the neurologic system could be involved?

1. Muscle: A problem with muscle function, termed a myopathy, can result in muscle atrophy. The most common cause of temporalis and masseter muscle atrophy in dogs is masticatory muscle myositis (MMM), which is caused from an immune mediated attack against the muscle fiber. This is a UNIQUE form of muscle inflammation because the proteins on these muscles are embryologically unique (2M fiber type) from all other muscles in the body. We care about that because it means that we can identify an antibody (AB) test that we can run that is highly specific AND sensitive! What else should we consider? Infectious myositis, secondary to neospora or toxoplasma infection would be my second choice differential for many dogs with this clinical presentation. In this scenario, the protozoa get into the muscle, set up a secondary inflammation (myositis) and muscle atrophy results. Sometimes you can see a mild positive on the aforementioned MMM AB titer test, but it is low, if positive at all. However, if you concurrently test for neospora and toxoplasma (serum titers) you can catch this "false" positive, and treat the correct disease.

Treatment for MMM: Immunosuppressive steroids for 30+ days, followed by a taper protocol.
Treatment for infectious myositis: clindamycin or sulfa antibiotics until negative or stable titers. This is often MONTHS of treatment!

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

Treatment for CN 5 deficits: this varies and is dependent on the underlying cause. It is a bit hard to summarize TidBit Tuesday-style. :) 

These cases can be puzzling to sort out so please reach out if you feel a neurologic examination is helpful for your patient. Have a great week!

Cervical Disc Herniation Associated Myoclonus in Dogs

Intervertebral disc herniation (IVDH) is the most common cause of cervical pain in small breed dogs. The most common clinical presentation is cervical pain with a normal neurologic examination, however in a few dogs gait deficits, paw replacement deficits, or reflex deficits can seen. Myoclonus, or a sudden onset, repetitive muscle contraction is seen in about 4% of dogs in a recent study from France. This muscle contraction is frequently confused for seizure behavior by clients so be on the look out for it! The classic presentation is a small breed dog that stops an activity, demonstrates myoclonus, and then resumes it's activity. Other signs of cervical pain (yelping, low head carriage, reduced range of motion) are often present when clients are questioned, so be sure to ask! 

What is the Significance of Cervical Myoclonus with IVDH?

The presence of myoclonus did not change the prognosis or outcome for the 20 patients in the recent study (JAVMA 2023: 261:4: 511-516.). Surgical correction resulted in less recurrence of signs, and immediate resolution in the post operative period compared to medical management. Approximately 25% of of medically treated dogs experienced another episode of myoclonus considered to be distinct from the original presentation. Medical management consisted of NSAIDs, gabapentin and, for some, tramadol. 

What is the Take Away?

• Myoclonus can occur with mechanical or chemical irritation of cervical nerve roots 

• Myoclonus does not affect prognosis

• Surgical management remains the recommended treatment for rapid resolution of signs of pain and reduction in relapse/recurrance

• French Bulldogs were over represented in this study!! (Again - See TidBit Tuesday in March for the list of Frenchie spinal cord diseases

As always, thank you for reading! I am thrilled to see the lovely weather on the horizon this week and hope you have a chance to enjoy some of it, too. 

Canine Myasthenia Gravis Update

What is myasthenia gravis?

Myasthenia gravis (MG) is a neuromuscular disease caused by congenital or acquired causes. Acquired MG is caused by an attack against the acetylcholine receptor on the muscle or  the muscle specific kinase (MUSK) protein. Acquired MG will be the focus of this TidBit today. 

How does myasthenia gravis present clinically?

Focal, generalized and fulminant forms have been described. Focal MG results in weakness of 1 or more muscle groups (ex: esophagus or pharynx) and does not cause limb weakness. Generalized MG results in limb weakness, with or without (usually with!) megaesophagus and pharyngeal weakness and the fulminant form causes acute severe flaccid paresis or paralysis often requiring hospitalization and intravenous intervention. 

How is myasthenia gravis diagnosed?

Acquired MG is diagnosed by a combination of clinical signs, positive acetylcholine receptor antibody titer and/or positive response to edrophonium challenge. A positive acetylcholine receptor antibody titer is considered the gold standard diagnostic tool.  Seronegative MG is reported in about 2% of cases and likely represents dogs with immune attack against the MUSK protein rather than the acetylcholine receptor. Edrophonium is a short acting acetylcholinesterase inhibitor that can be used in the preliminary stages of diagnosis. Animals are administered a small dose of edrophonium and monitored for clinical signs of improved strength. This test is not advisable for use in obtaining a diagnosis of focal MG. It is important to note that dogs with other neuromuscular diseases may have a positive edrophonium challenge therefore it should not be used as a sole diagnostic tool. 

What is the treatment for myasthenia gravis in dogs and cats?

Acquired MG is most often treated with an oral, long acting acetylcholinesterase (pyridostigmine). Signs of overdose are similar to signs of acquired MG (SLUD plus weakness) therefore it is recommended to start at a lower dose and slowly increase the dose over 1-2 weeks until clinical signs resolve. Immunosuppression has been used for pets with focal or generalized MG however the risk of secondary pneumonia is higher with immunosuppression and the clinical improvement does not appear to be better than with pyridostigmine administration therefore it is rarely recommended. 
Acquired MG will often result in remission within 8 months of the initial diagnosis. If remission is not achieved, follow-up testing for concurrent diseases that could trigger MG is recommended. This includes a thyroid panel (for thyroiditis), chest radiographs and abdominal ultrasound for a cancer screening. 

Thanks for reading! I hope you have a great week and I look forward to working with you soon. 

Cushing's Induced Muscle Weakness

Hyperadrenocorticism (HAC) or Cushing’s disease is a common cause of muscle weakness. Biopsies have shown that type II muscle fiber atrophy is common and clinical signs have included weakness in all four limbs, along with muscle atrophy. A less common form of HAC myopathy is a severe muscle stiffness (SMS) that results in a stiff or stilted gait. A recent study evaluated the signalment, presentation and treatment options along with long-term outcome in a collection of 37 dogs diagnosed with HAC.

What is HAC induced Severe Muscle Stiffness?

As the name suggests, the clinical manifestation of the unusual form of HAC myopathy includes stiffness of pelvic or all four limbs. The etiology is unknown but electrodiagnostic evaluation suggests a myotonia. Myotonia is defined as a sustained contraction after percussion (hammer reflexes) or voluntary contraction. The muscle will occasionally ripple visibly, but usually a prolonged limb stiffness can be seen. Dogs with HAC induced SMS have a ridged, stiff-legged gait when moving and don’t demonstrate appropriate joint flexion. According to Golinelli et al (DOI: 10.11.11/jvim.16620) over 60% of dogs had only the pelvic limbs affected at the time of diagnosis, the remainder had all four limbs affected. An elevated CK was noted in 75% of the dogs, suggesting muscle membrane breakdown or injury.

It was interesting to note that the diagnosis of SMS was more common in small breed dogs, weighing less than 15 kg. The time of SMS diagnosis varied in reference to the HAC diagnosis.  Almost 62% were diagnosed 1 month to 3 years after being diagnosed with HAC, 8% were diagnosed with HAC and SMS at around the same time and 30% were diagnosed with SMS 1 month to 1 year BEFORE being diagnosed with HAC. There are many reasons for these findings including owner or veterinarian awareness of SMS, lack of ability to test for or diagnose HAC, or perhaps a pathologic change/trigger required to convert from HAC with weakness to SMS.

How is it treated?

In short, poorly. In the report cited above, no single treatment resulted in effective resolution of the clinical SMS. Therapeutic intervention included benzodiazepine drugs (19% of cases), physiotherapy (16% of cases), acupuncture (5% of cases), and one or two dogs received mexiletine, NSAIDs, dantrolene, botulin toxin, L-carnitine, methocarbamol, gabapentin, and cannabinoids. Mild improvement was reported with some treatments. Survival of dogs with HAC induced SMS was unchanged compared to survival of dogs with HAC only.

Key points:

Be aware that SMS can occur with HAC

The reason a dog will have SMS instead of muscle weakness is unknown

No specific treatment resolved signs in all dogs, however there are several reasonable treatment choices listed above to try.

Thanks for reading! Enjoy the first day of Spring!

Cluster Buster Protocol

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

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

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

• If a patient has a history of 2 or more episodes of cluster seizures

• If the patient has a history of status epilepticus 

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

Levetiracetam

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

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

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

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

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

Midazolam

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

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

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

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

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

Summary
Providing options at home for cluster seizure care can reduce the need for hospitalization, and clinic visits. Additionally, any of the above treatments can be provided in hospital during seizure observation should that be needed. All the treatment choices discussed above are targeted for dogs and are rarely used in cats.

I hope your Tuesday isn't a cluster of craziness! As you well know, I enjoy helping you, help your patients with seizures live their best lives so please reach out if you're working through a case and need a little extra help. Have a great week!

Pug Myelopathies

Did you know that Pugs are commonly diagnosed with T3-L3 myelopathies? There are so many to chose from I thought I'd take this TidBit Tuesday and discuss some of the more common ones. 

Intervertebral disc herniation

Dis herniation is a common etiology of a T3-L3 myelopathy in many dogs, and Pugs are no exception. Type I and Type II disc herniations have been diagnosed in Pug dogs in the thoracolumbar region. Clinical signs include acute (or chronic if type II) variably painful (but often WITH signs of discomfort in this breed), pelvic limb proprioceptive ataxia followed by paraparesis. Signs can progress to paraplegia with loss of deep pain. Surgical and medical correction have been shown to be useful for Pug dogs and depend on the severity of the clinical signs.

Subarachnoid diverticulum

Subarachnoid diverticulum (SAD) can be described as cystic accumulations of fluid in the subarachnoid space around the spinal cord. Pugs are cited as among the most common breeds to be diagnosed with SAD. Clinical signs are slow in onset and often include incontinence early in the clinical course. Dogs with SAD are not typically painful. Medical and surgical management have been tried however neither approach appears to be an overwhelming success. Medical management is typically my preferred approach. 

Meningomyelitis and Neoplasia

Any and all breeds are at risk for these two diseases and Pugs are not overrepresented in this group. That said, clinical signs would include acute or chronic onset of signs with paraparesis and proprioceptive ataxia in the pelvic limbs. Treatment is medical for meningoencephalitis and medical, surgical or with radiation therapy for neoplasia. 

Degenerative Myelopathy

Degenerative myelopathy (DM) is caused by a genetic predisposition to demyelination of the T3-L3 spinal cord segments. Pugs are over represented and either confirmed or strongly suspected to have a mutation of the SOD1 gene (I cannot remember if it has been confirmed, yet!), like  German Shepherd dogs. Clinical signs include a slowly progressive, non-painful, proprioceptive ataxia that progresses to paraparesis, then paraplegia. If not euthanized, pets can progress to tetraparesis and eventually respiratory failure. A diagnosis is made through findings of a normal MRI and CSF analysis along with appropriate clinical signs. Genetic testing can be useful but isn't a stand alone test. 

Constrictive myelopathy

This is the new kid on the block. First published several years ago, constrictive myelopathy is caused by a fibrous band of tissue that circles the spinal cord and causes a constriction to CSF flow and compression of spinal cord tracts. Constrictive myelopathy is now thought to form due to a lack of development (hypoplasia) of the articular processes of the TL vertebra. If you imagine the articular processes are the "hands" that hold the vertebra together, supported by muscles and ligaments, becomes easy to see how hypoplastic articular processes might result in vertebral instability. This instability would then result in fibrotic tissue forming to help "stabilize" the joint. Sadly, this fibrous tissue then causes spinal cord constriction. To make matters worse, SAD can also form secondary to chronic spinal cord trauma so these poor dogs can have constrictive myelopathy secondary to hypoplastic facets and SAD in their T3-L3 spinal cord segments. Yikes. A diagnosis is made on MRI. A recent study (https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.16639?) evaluated the incidence of constrictive myelopathy alone, or in combination with other spinal cord diseases in a group of Pug dogs. They found only constrictive myelopathy in 3 dogs, constrictive myelopathy combined with IVDH in 17 dogs and IVDH only in 9 dogs, IVDH + SAD in 2 dogs and articular process dysplasia in ALL 32 dogs!

Summary:
Pug dogs are at risk for many causes of paraparesis and proprioceptive ataxia. A detail neurologic examination, history , and appropriate diagnostic imaging and spinal tap can help determine the underlying etiology and subsequently direct treatment most specifically. 

I hope this TidBit doesn't give you the impression that I am anti-Pug - I adore these little dogs. BUT,  I recognize their predisposition to specific spinal cord diseases when assessing them clinically. Remember, not all dogs with pelvic limb weakness have a disc herniation! 
Have a great week!

Hypophosphatemia in Seizures Vs. Syncope

We've all been there, right? An elderly small breed patient with a grade II or III heart murmur presents to you with a history of "passing out". Clients aren't more descriptive than that, and they didn't catch a video. Is this syncope or was this a seizure?

You have several things to ask and look for (see prior TidBit Tuesday on syncope) but recent research has given us one more tool in our belt to help differentiate between these two diseases. 

Human patients with generalized tonic-clonic seizures demonstrate a reduced phosphate level within several hours of the event and patients with syncope do not. A study from Israel published data in January that strongly suggested a link between hypophosphatemia and seizures in dogs, as well. According to this study, 87 dogs with seizures and 26 dogs with syncope were included. Phosphate was evaluated within 3 hours of the "event" in question and noted to be decreased in 28 (32%) of dogs with seizures. None of the dogs with syncope had a low phosphate level. Dogs were excluded from the study if their creatinine was above the normal range to eliminate those cases with hypophosphatemia from renal causes. Median phosphate levels were significantly different between the two groups!

Key point: With an optimum cutoff value of 0.97 mmol/L (about equal to 3.0 mg/dl), evidence of hypophosphatemia has a 100% specificity and 44% sensitivity to diagnose seizures. 

Importantly, this tool should not be used as a stand alone finding to differentiate between seizures and syncope! However, identification of hypophosphatemia, within 3 hours of the witnessed event, could suggest a generalized seizure was more likely than a syncopal event if all other historical, physical examination and biochemical findings are concurrently evaluated. Important note: This has not been verified in dogs with focal seizures or complex partial seizures OR cats! 

This week's TidBit Tuesday is short and sweet. I hope you have a wonderful start to March 2023! 

Reference: https://doi.org/10.1016/j.tvjl.2022.105914

Horner's Syndrome and Cervical Myelopathies

Do any of you feel comfortable localizing Horner’s syndrome in a dog? If you do…skip the first section and read the data from a recent study about cervical myelopathy and Horner’s syndrome.  If not, please carry on and join us for an interesting look at Horner’s syndrome with cervical myelopathies.

 
First, Anatomy

The sympathetic pathway to the eye is a 3-neuron system. Neuron 1 starts in the thalamus, travels through the brainstem and cervical spinal cord to T1-T3 thoracic spinal cord segments where it synapses. Neuron 2 starts here and travels cranially, through the ansa subclavia along the vagosympathetic trunk (right next to that jugular vein you’re about to do venipuncture on!) to the caudal aspect of the bulla. From there, the 3rd order neuron takes a path through the tympanic bulla, along the ventral aspect of the skull (in the cavernous sinus) and hops a ride with CN 5 (trigeminal) to make a beeline to the eye. This neuron innervates the muscles of the iris, eyelids and orbit. It is the most indirect path anyone could design but I might argue that you can break it down into several key parts when localizing Horner’s Syndrome.

• Intracranial

• Cervical

• Brachial plexus

• Jugular groove

• Tympanic bulla

• CN 5

Cervical Myelopathies and Horner’s Syndrome

After reviewing the anatomy, it might be easy to see how a cervical lesion may cause Horner’s syndrome, right? The 1st order neuro travels from the intracranial structures via the cervical spinal cord to the upper thoracic spinal cord segments. Interestingly, a recent study looked at Horner’s Syndrome and cervical myelopathies* and found an incidence of only about 10% of Horner’s syndrome with concurrent cervical myelopathy. Therefore, although the anatomy makes sense, it is a fairly protected neuronal pathway and therefore a cervical lesion rarely causes Horner’s signs.

What Causes Horner’s Syndrome and a Cervical Myelopathy?

I’m glad you asked! According to this study, more dogs with Horner’s syndrome had noncompressive lesions compared to the control group (dogs with cervical myelopathy without Horner’s syndrome). Noncompressive lesions are often caused by fibrocartilaginous embolism (FCE) but hydrated nucleus pulposus extrusion (HNPE) and intramedullary neoplasia, noncompressive spinal trauma, Syringohydromyelia and inflammatory myelitis were found to cause Horner’s syndrome.  Also of note, Horner’s syndrome can be unilateral OR bilateral with cervical myelopathies.

Did having Horner’s Syndrome Affect Prognosis?

Nope. The underlying disease predicted prognosis and having Horner's Syndrome did not significantly negatively or positively influence outcome. However, seeing Horner’s syndrome on the neurologic examination would suggest that a surgical lesion is less likely to be identified.

 
Do you have a patient with Horner’s Syndrome? Do you suspect a cervical myelopathy? I’d love to help! Please reach out via email or schedule a consult online. Stay safe on these slippery roads and have a great week!

Reference from the TidBit Tuesday: https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvim.16588

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!

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!

Idiopathic Geriatric Vestibular Disease of Dogs

Idiopathic Geriatric Vestibular Disease

If I had a dime for every time a client told me their dog had a stroke (usually "several years ago") and that they suddenly were dizzy, and then, suddenly got better, I'd be rich. Or at least I could by myself a soda. :)

Idiopathic Geriatric Vestibular Disease is Not Caused by a Stroke

Human strokes happen suddenly, and can cause signs such as hemiparesis, hemifacial weakness, and often resolve over time so it is reasonable that a stroke would be confused with the canine idiopathic geriatric vestibular disease (IGVD). But they are different! Strokes occur at the level of the brain, brainstem, or cerebellum, and IGVD localizes to the peripheral vestibular system. 

What is Idiopathic Geriatric Vestibular Disease?

As the name implies, we have yet to find the etiology. Several proposed causes have been postulated but none confirmed. Clinical signs include:
1) Acute onset vestibular signs (head tilt, nystagmus, vestibular ataxia, positional strabismus)
2) NO evidence of ipsilateral hemiparesis (weakness on the same side as the head tilt)
3) NO evidence of ipsilateral paw replacement deficits. Some older dogs have unrelated or preexisting paw replacement deficits. If the deficit involves both pelvic limbs, equally, or a contralateral limb to the head tilt, the odds are strong that the deficit is unrelated to the vestibular signs. 
4) NO mentation changes (obtunded, stupor, coma).
5) NO evidence of hypothyroidism, otitis media/interna, neuritis or peripheral/ear neoplasia 

Options 2-4 above help you localize the lesion to the peripheral system, but that is just a localization. Options 1 and 5 help you eliminate the other differential diagnoses that could also cause peripheral vestibular disease and thus, narrow the diagnosis to idiopathic geriatric vestibular disease. 

Treatment

Treatment for IGVD is supportive. Steroids, antibiotics and NSAIDs do not improve clinical signs. Signs typically begin to resolve within 48 hours of the onset, and have reached a state of stability by 30 days. The most marked improvement typically occurs in the first 14 days. Supportive care with anxiolytics (diazepam, trazodone, other), antivertigo drugs (meclizine, ondansetron), and nutritional support may allow the animal to be more comfortable during the recovery process. Clean, dry bedding with frequent comfort checks are important for non-ambulatory dogs to minimize bed sores and other complications. 

Prognosis

Dogs with IGVD have some of the most severe clinical signs but have a very good long-term prognosis! Intensive supportive care is important in the first few days. Most dogs will recover to a functional state within 1 week and return to baseline within 30 days. Importantly, the head tilt is often permanent!! Please be sure to inform clients of this, otherwise they may think the dog is still clinically affected months and years after the signs have otherwise resolved. 

Please let me know if you have a dog with vestibular disease that you feel would benefit from an evaluation. I look forward to working with you soon.  Have a great week!

Levetiracetam use in Cats

We all know cats are not small dogs, so how does levetiracetam (leh-vuh-tr-A-suh-tam) differ between species?

Metabolism
The mechanism of action (modification of the SV2A receptor) is the same for cats and dogs. This mechanism of action (MOA) is unique to levetiracetam and different that the MOA for phenobarbital. 

Formulations
There are two formulations available 1) standard release (SRL) and 2) extended release (XRL). The dosage of 20 mg/kg PO q8h for the SRL formulation, comes from pharmacokinetic analysis of this drug in a cohort of healthy cats. A therapeutic range has not yet been developed for cats therefore if seizure control is poor, the dosage is often increased until signs of toxicity are noted and then reduced to the highest effective dose with minimal side effects. When doing that, the prescriber is using the individual animal as a guide for toxicity rather than an established therapeutic range. Reported side effects include hypersalivation (mild, transient), inappetence and mild lethargy. There are very few efficacy studies for cats, however in 2008, a single study reported a greater than 50% reduction in seizures  in 7 of 10 cats when levetiracetam was added to phenobarbital. Liquid formulations are readily available through compounding pharmacies and can be used interchangeably with the 250 mg size tablets. Use caution when prescribing the liquid formulation to ensure it does not have xylitol as an added ingredient. 

Extended release levetiracetam is available in 500 mg and 750 mg size tablets. Historically, this has limited its use in cats. In 2017, I decided it was high time we changed that thinking so we evaluated the pharmacokinetics of a single dose of 500 mg XRL in healthy cats and found that it was well tolerated with minimal side effects. Furthermore, we identified that a reduce dosing interval from q8hr (SRL) to q24h when using XRL was appropriate for cats! The serum levetiracetam concentrations were really high therefore we subsequently evaluated the use of levetiracetam over 10 days to monitor for drug accumulation. Thankfully, none was identified! No efficacy studies have been performed using 500 mg PO XRL q24h in cats, to date, however I do recommend this dosage for cats, when levetiracetam is needed and q8h dosing isn't an option.

The story doesn't end there! Medicating cats is such a terrible thing to do to a cat (and horrifying for some owners) that I then explored the idea of transdermal levetiracetam (TD).The dosage of 20 mg/kg transdermal q8h resulted in serum concentrations similar to those of the oral route with minimal side effects. We have not evaluated TD levetiracetam long-term so efficacy remains unknown. Do I use TD levetiracetam? Yes. I ensure that the clients know that this is cutting edge research and therefore long-term efficacy studies have not been performed; purely that it is well tolerated. 

That's all for now! Please reach out with any suggested topics and stay tuned for a super fun neurology CE event coming this summer. Shhhh...it's still in the planning stages! 

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

Thank You and Happy New Year!

This final week of 2022, I am thinking of you and your staff.

• Thank you for trusting your patient's care to me. I am humbled by the kindness, consideration and feeling of welcome that I receive when I enter your clinic to help care for your patients.

• Thank you for having kind, knowledgeable staff to assist me.

• Thank you for giving up valuable floor space (rooms, hallways, office space or even bathrooms!) to allow me to fully examine your patient.

• Thank you for the insight, nuance and personal touch you add when sharing information about a client or patient. I love being a part of your team. 

• Thank you for being an advocate for your patient and for including me in their health care needs. 

• Thank you for following up with me, giving me feedback, patient updates and answering my emails when I check in. 

Most of all, thank you for being you!

Many of you I now call friends. I look forward to seeing you and your staff when I get that "ping" on my phone that signals that a consult was scheduled. Keep up the good work. You are valuable and important.  

If you missed a TidBit Tuesday, or misplaced an email, you can always find them on the blog at https://barnesveterinaryservices.com/new-blog. I'm always happy to add new subscribers so don't forget to sign up new vets in your practice!

Happy New Year and thanks for reading. :)