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. :)

Myoclonus - what does it mean?

Myoclonus is defined as a sudden onset jerking motion. How is this different from a tremor? Tremors tend to have a creshendo, decreshendo appearance where as myoclonus has been described as "square form" impulse with sudden, rapid onset, sustained contraction, and sudden stop. Okay, fine, it's not a tremor. How do I diagnose myoclonus? 

There are four common types:
1) Physiologic - the classic example is hiccups.
2) Epileptic- occur with or around epileptic seizures
3) Idiopathic - unknown origin or cause (rare in veterinary medicine...or we're just missing it.)
4) Symptomatic - due to an underlying pathology. For example, distemper virus. 

Neuroanatomic lesion localization:
1) Cortical - usually associated with myoclonic seizures. 
2) Subcortical (brainstem) - "falling asleep" myotonia. In this case, people or animals will suddenly "jerk" just as they fall asleep. Classically, this has been thought to occur because the cortical functions "turn off" before the brainstem functions but this may not be the complete story. 
3) Peripheral - an example is hemifacial spasms, or ocular spasms (have you ever had your eyelid  twitch annoyingly and you cannot stop it?)

Veterinary neurologists are often consulted for symptomatic and epileptic myoclonus. Although there is a population with idiopathic myoclonus, it is rare. Symptomatic myoclonus occurs at rest, asleep, or during motion. Symptomatic myoclonus does not stop with sleep! The animal may appear aware or unaware of the twitch. If the contraction is happening in a body part used for walking or eating it may be life limiting. If not, animals may live with a myoclonus with minimal disruption. Epileptic myoclonus occurs around a time of seizure activity and is therefore often managed with anticonvulsant management.

Distemper virus is a common cause of canine myoclonus and CNS infections (various causes) have been cited as causes of feline myoclonus. There is no treatment available for distemper virus therefore, patients are monitored for progressive neurologic signs (mentation changes, gait changes, seizures, other) and euthanized if signs are progressive. If the signs are not progressive, usually myoclonus is not a reason for euthanasia. 
That's all I have for you today! I hope you enjoyed this TidBit about myoclonus and feel better prepared when you see it in your exam room. :)

Thank you for reading! May you have a wonderful, twitch-free holiday week! 

Neuroanatomic Lesion Localization Practice book!

It's Here! The Small Animal Neuroanatomic Lesion Localization Practice Book by yours truly!

It's always hard to self promote, so instead I wish to draw your attention to the many neurologists that contributed cases that made this little workbook the workhorse that it is.
1. Dr. Helena Rylander (UW-VC neurologist)
2. Dr. Joy Delamaide-Gasper (MVS neurologist)
3. Dr. Kari Foss (U of I neurologist, and former student)
4. Dr. Devon Hague (U of I neurologist)
5. Dr. Julien Guevar (Swiss neurologist and former UW-VC Neurologist)
6. Dr. Susan Arnold (U of Minnesota Neurologist and UW- VC graduate)
7. Dr. Sam Long (Australian neurologist and all around amazing guy)
8. Dr. Simon Platt (Forum UGA neurologist and ACVIM-Neurology past president)

The Small Animal Neuroanatomic Lesion Localization Practice Book is just that - a practice book - geared for general practitioners, students, and interns who are interested in brushing up or dusting off their neuroanatomic lesion localization skills. This little ditty has 7 chapters, with many cases in each chapter for you to try your hand at neuroanatomic lesion localization.

Not enticed enough?? If you get stuck - you know the author of the book and can email me directly for help! (yay for connections!)

Still not enticed?? Check out this link to see more: https://www.cabidigitallibrary.org/doi/10.1079/9781789247947.0000
Cost $65 USD

Note: I don't get any notifications of who buys a book, but if you suddenly stop consulting I'll assume you bought the book and learned it all and no longer need me. I really should stop trying to teach myself out of a job.... :)

That's it for this week. Not a typical TidBit per se, but hopefully you don't mind so much. Thanks for reading!
Have a great week!

Bruxism and Forebrain Disease

Bruxism is defined, in human medicine, as repetitive, involuntary, masticatory muscle activity, often appears as grinding teeth, bracing or thrusting of the mandible. There are two types: awake and asleep. Asleep bruxism is quite commonly reported in humans and can be triggered by stress or anxiety. Awake bruxism, or uncontrolled bruxism during awake states, is a very different thing. Awake bruxism (AB) can be broken into pathologic or physiologic causes. Physiologic causes don't apply to veterinary medicine so let's dig deeper into pathologic, awake bruxism. Within the pathologic group there are idiopathic causes and symptomatic causes. Neurologic diseases such as inflammatory conditions, traumatic or congenital disease, epilepsy and a host of other causes have been reported to be associated with awake bruxism in humans. A recent article, published in the JVIM, noted that bruxism secondary to a neurologic cause is most commonly awake bruxism.

Have you seen a dog with Bruxism? The recent article by Liatis T, et al, evaluated AB in 4 dogs over a span of 11 years so don't feel badly if you've not seen one! A link to the entire report is found at the bottom. Although previously reported in dogs with congenital storage disorders, it is rare in mature adult dogs. In this study, two dogs were presented by the owners with a complaint of AB, along with other clinical signs of neurologic disease. AB was noted in the second two dogs by the attending clinicians during evaluation. AB was episodic in all four dogs, occurring throughout the day and always stopped when distracted. No post ictal signs were noted and no autonomic signs were seen during or after the event. All four dogs had forebrain lesions!

Take away: If you evaluate a dog for awake bruxism, or if you note it during the exam while evaluating the pet for other neurologic abnormalities, consider it abnormal. It is not pathognomonic for forebrain disease but, at least according to this report, is strongly supportive of a forebrain lesion. This may be an indication to get a neurology consultation and advanced imaging.

Link: https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.16570?campaign=wolearlyview

Thanks for reading! I look forward to working with you again soon.

Exercise and Seizure Control

Last year we talked about a temporal relationship between seizures and exercise. It has been shown that seizures rarely occur DURING exercise.

Recently, I was involved in a study, performed at the University of Wisconsin, evaluating increased activity and it's relationship to seizure development. In this study, dogs were tracked using a FitBark(tm) exercise tracker for 3 months and then prescribed a 20% increase in activity over the next 3 months. Seizure frequency and "seizure days' (the number of days that a dog has a seizure) per month were evaluated. Unfortunately, many of the dogs did not actually do the exercise increase as prescribed (ugh!) but even accounting for that, exercise was not associated with a statistically significant reduced seizure frequency or number of seizure days during the study period.

Why didn't this work? There are many possible reasons why prescribed exercise didn't change the seizure frequency. The most obvious reason is that not enough pets made the change to show a statistical difference. The other, more concerning option, is that exercise really doesn't have an effect on overall seizure performance. There are mixed results in the human epilepsy studies. Although it is rare to have seizures during activity, it can happen. Furthermore, some studies showed a lower seizure frequency when exercise was added to a treatment plan and other studies did not.

What is the take home message? Increased activity cannot (yet) be used as an adjunctive treatment for seizure management. It is still a healthy choice, and should be encouraged in all pets but especially our dogs with epilepsy but not, sadly, as a means to seizure control. This was a small study, so my hope is that future studies will yield more robust results.

Thanks for reading! If you want to read the whole study you can find it here: https://onlinelibrary.wiley.com/doi/epdf/10.1111/jsap.13568

Have a great week. Happy Thanksgiving! Enjoy exercising with your pets, friends, and family this holiday week!

Dogs Fall in the Fall

Today, you're presented with a 4 year old German Short-Haired Pointer with a history of rapidly progressive difficulty walking. Although your heart rate may be going up when you read this on your schedule, you're calm, cool and collected as you pick up your pleximeter and head into the room.

Your technician has provided the following history for you: The pet was out hunting last weekend with the owner and no unusual circumstances occurred. He did run away two days ago and came back with a small bite wound on his muzzle. The pet is up-to-date on vaccination (including rabies) and has not had any change in voiding habits prior to the last 24 hours. The dog is fed a mixture of a commercial kibble diet and raw meat. There is no reported prior medical history. 

Physical exam: Unremarkable other than the bite wound. It is healing, not infected (visual inspection only) and does not appear to be bothering him. He is his typical, high strung, friendly self!

Neurologic examination:

Mentation: BAR

Cranial nerves: normal

Postural reactions: Absent in 3 of four limbs, reduced in right front limb only. 

Reflexes: Absent patellar reflexes bilaterally, absent withdrawal reflexes in both pelvic limbs (but he howled pitifully when you tried to do it!) reduced withdrawal in both thoracic limbs, more notable on the left thoracic limb than the right. Absent cutaneous trunci reflex to T6 on the left, and reduced to T/L junction on right. 

Palpation: non-painful on palpation but hyperesthetic when trying to do reflexes. This is unusual for him as he doesn't typically mind his feet touched or even flinch during vaccinations. 

 Gait: Non-ambulatory tetraparetic with paraplegic (no motor observed in PL), marked paresis in both thoracic limbs, more noted in left than right. 

Neuroanatomic lesion localization:

First, decide if this is brain or spinal cord.

1. Brain: With reduced reflexes, it isn't a brain problem.

2. Spinal cord: It could be a spinal cord problem, but then it must be localized to BOTH C6-T2 and L4-S3 (entire plexi for both sites) and, although possible, it is highly unusual. If that is where we localize the problem, how do we account for the c. trunci reflex? Based on the findings, it should suggest a lesion mid thoracic lesion (1-2 segments cranial to the cranial most reflex) and that doesn't fit in either C6-T2 or L4-S3 segments, does it? No. Therefore, this isn't a spinal cord problem either. This is neuromuscular, my friends!

Neuromuscular neuroanatomic lesion localization.

We can narrow it down further within the neuromuscular localization. You have 3 choices: 1) Muscle 2) neuromuscular junction and 3) nerve. Dogs with myopathies (muscle disease) have normal reflexes (and he doesn't) so it isn't a myopathy. Dogs with disease of the neuromuscular junction have absent reflexes (and he does), so it could be this. Dogs with a peripheral neuropathy often have patchy loss of reflexes (and he does) so it could be this. Therefore, you would suspect either a neuromuscular junctionopathy or peripheral neuropathy in this dog. 

Differential diagnoses:

1. Junctionopathy - botulism, tick paralysis, coral snake envenomation, Ca blockers, acute myasthenia gravis (rare).

2. Acute peripheral neuropathy - hypothyroid crisis, polyradiculoneuropathy (APN), autoimmune (rare). 

Of these, the most likely is APN (Coonhound paralysis) based on the dog's history, neurologic exam and signalment. 

Although an ELISA test does exist (Developed at UW-Vet School), it has a long turn around time and therefore isn't terribly useful for the initial diagnosis. I find it helpful to rule out the other causes rather than focusing on diagnosis this cause. I suggest applying a tick repellant (rule out tick paralysis), submitting a myasthenia titer, checking CBC, serum biochemistry for signs of biochemical imbalance (calcium specifically) and a T4. If all of this is normal, we're likely back to acute polyradiculoneuropathy (APN). 

Treatment is purely supportive. This disease is caused by an autoimmune attack against the nerve roots triggered by many things, including racoon saliva. Yes, saliva. Interestingly, a report in 2019 found an association with the consumption of raw meat contaminated with Campylobacter jejunii within 7 days of the development of APN. Antibodies are available and can be administered in the early phase but may not be available in your area. Supportive care includes ventilatory monitoring and mechanical ventilation as needed (they can loose the ability to contract the intercostal muscles and therefore cannot inhale), nutritional support (they can eat, drink and void voluntarily but need to do so sternal and be cleaned frequently to avoid bedsores), and nursing care (see prior). Signs reach peak severity within 10 days for most dogs. Signs typically improve within 3 months (12 weeks).  Please note that this disease is very recoverable with appropriate nursing care but it takes long, and intensive, at home nursing care. Sadly, affected dogs do not gain a sustained immunity after they recover and can show signs again if they are exposed to an appropriate trigger. 

Please let me know if you have any questions about today's TidBit Tuesday. I hope you have a great week!

Masticatory Muscle Myositis: That's a mouthful!

We are seeing more cases of masticatory muscle myositis lately so I thought we'd look into this interesting diagnosis together. Let's start by defining it.
Masticatory Muscle Myositis (MMM) is an inflammatory, autoimmune myopathy affecting the muscles of mastication (temporalis, masseter, pterygoid and rostral digastricus). All of these muscles are innervated by CN 5, specifically the mandibular branch.

Why only these muscles?
The muscles listed above have a specific myofiber type (type 2M), which is only present in these muscles and some fetal muscles. All other muscles in the body are 1A and 2A fiber types! Therefore, these muscles present a unique antigen for the immune system to target.

What does the clinical picture look like?
There is an acute phase, and a chronic phase. The acute phase occurs first and often includes signs such as jaw pain, swollen muscles, and difficulty chewing. (Note NOT drop jaw or difficulty closing the jaw....that is a different disease.)
If left untreated, patients will then progress into the chronic phase, which includes signs such as muscle atrophy and an inability to open the jaw. Muscle fibers are replaced with scar tissue during the chronic phase making the dog unable to open their mouth more than a few centimeters over time.

Must we take a chunk of muscle to make this diagnosis?
No, you don't! Although you will obtain a diagnosis in both the acute and chronic phase, there is an easier, and less invasive, way. The serum 2M antibody test is both highly sensitive (85-90%) and highly specific (100%) and is the preferred diagnostic test for MMM. Send it to the Comparative Neuromuscular Lab in La Jolla CA (https://vetneuromuscular.ucsd.edu/) if you live in the states. I think there are other choices worldwide but I'm not as aware of those.

Steroids are the best, and most effective treatment.
Immunosuppressive steroids are the most effective treatment for this disease and are strongly recommended in the acute phase. Your goal is to stop that inflammation in its tracks so that the patient doesn't progress to the chronic phase. Once they replace the muscle fibers with connective tissue, the game is over. The dog cannot open its mouth, chew, or be safely intubated or vomit. The chronic stage results in poor quality of life. Steroid protocols vary by neurologist. My protocol starts with 1 mg/kg PO q12h prednisone for 30 days, and then tapers slowly from there. Repeat 2M antibody titers every 1-2 months is recommended. Once the numbers return to normal, it is generally safe to stop the steroid administration.

If any dog has painful muscles of mastication, struggles to open its jaw without pain, and has an elevated CK on lab work a 2M antibody titer is recommended. Don't forget: neospora caninum and toxoplasma gondii can cause myositis and do attack the muscles of mastication. Concurrent testing for these two diseases in all dogs is strongly encouraged before starting immunosuppressive prednisone. I have been taken by surprise how often these tests are positive when I suspect this is "just" MMM.

Hopefully this helps you address muscle pain in your patients. If you have a question about a patient, please contact me via email or schedule a consultation online! Have a great week!