Myasthenia Gravis in Cats

What is myasthenia gravis?

Myasthenia gravis (MG)  has two forms: 1) congenital and 2) acquired. Acquired myasthenia gravis is more common and results from the development of antibodies against the nicotinic acetylcholine receptors on the muscle membrane. 

What is the clinical presentation?

Cats present commonly with the generalized form which includes a wide variety of clinical signs and progressions. This may include weakness (the "floppy cat"), cervical ventroflexion, or pharyngeal weakness. Signs may be slowly or rapidly progression and even result in waxing-waning clinical signs. 

What causes the acquired form of myasthenia gravis?

Most cats have an idiopathic MG however up to 30-50% of cats will develop paraneoplastic MG for which thymoma are commonly implicated. Spontaneous remission of idiopathic MG within 6-8 months is common in dogs, but was previously thought to be uncommon in cats. A 2019 article found remission within 6 months in ALL 8 cats evaluated. (Mignan T, et al. JVIM Nov 2019) Remission even occurred in several cats that didn't have any form of immunosuppression or acetylcholinesterase inhibitors prescribed (see treatment below). 

How should I diagnose myasthenia gravis?

1. A thorough neurologic exam for appropriate lesion localization (yay!), and
2. An acetylcholine receptor (Ach-R) antibody titer through a reputable lab. Here in the states, I recommend Dr. Shelton's lab (http://vetneuromuscular.ucsd.edu/). This titer can be repeated to document biochemical remission along with the neurologic exam to document clinical remission. 

What is the ideal treatment?

Oh, the million dollar question! Based on experience I'd say cats respond less favorably to acetylcholinesterase inhibitors (think pyridostigmine or edrophonium) and therefore immunosuppressive steroids have been my go-to treatment. Having seen the data on spontaneous remission, I might consider no treatment in a minimally affected cat.

What is the long-term prognosis?

Idiopathic myasthenia gravis carries a good prognosis in cats. Should pharyngeal weakness become a clinical problem, aspiration pneumonia may result in increased morbidity or mortality. The 2019 study by Mignan et al reported a 100% survival at 6 months, without signs of relapse up to 4 years after treatment. Cats with paraneoplastic myasthenia gravis have a poorer short and long-term prognosis. 

Key Points:
1. Cervical ventroflexion, or a "floppy" cat on examination should prompt an Ach-R antibody titer for myasthenia gravis diagnosis. (Maybe even a neurology consult!)
2. Treatment could be immunosuppressive steroids OR no treatment at all if clinically mild
3. Prognosis is good if a thymoma or other neoplastic process is not identified. 

Thanks for reading! Happy 4th of July to US folks reading and Happy July 1st to Canadian folks! The rest of ya - hope you're having a good week!
Also, I'm looking for a location that can hold up to 20 people for a possible CE event in February 2025 in the middle of the state (Portage/Dells/Stevens Point). Do you have a hospital conference room I could rent or do you have a reocmmenation for a conference center that you thought did a good job in that area? Please reach out if you do!

Hypothyroidism and Neuropathies

Does hypothyroidism affect the nervous system? You bet! The peripheral nerve is the most common target in the neurologic system. How does a low thyroid hormone affect the peripheral nerve (you might ask)? I'm glad you asked...

Etiology:

1) accumulation of mucinous deposits resulting in nerve entrapment
2) demyelination secondary to Schwann cell defect
3) vascular nerve damage secondary to hypothyroid induced dysfunction of BBB
4) disruption of axonal transport

Signalment:Typically older dogs, however congenital disease does (rarely) happen. NOTE: dogs are not always overweight, heat-seeking or have flaky-hair coats with peripheral neuropathy signs. 

Clinical signs:A polyneuropathy (multiple nerves affected) is most common. This results in paresis without ataxia and reduced to absent peripheral spinal reflexes. Signs may be mild, to start. 
Cranial nerve deficits such as facial nerve paralysis (VII), vestibular dysfunction (VIII), or laryngeal paralysis (X) are common signs of hypothyroidism. Of course, other things can cause damage to these nerves but don't forget to include hypothyroiism on your differential diagnoses list for patients with a peripheral neuropathy. Hypothyroidism may also cause a myopathy and/or megaesophagus.

Diagnostic tests:T4 is a good first step. If abnormal, a full panel is recommended. 

Treatment options:You guessed it...supplementation!

Prognosis:The neuropathy is likely to improve a little or a lot, after several months with therapy if the axonal degeneration is not too severe. I commonly caution owners to be prepeared for perminent deficits and rejoice when that doesn't happen!
Cranial nerve deficits may persist even with appropriate treatment.

Frequency:
Common in older dogs. Remember they don't need to be over0-weight, heat seaking or even sluggish to get a hypothyroid induced peripheral neuropathy. Cats can be hypothyroid too!

May the luck of the Irish be with you this week! Thanks for reading and have a great week! 

Limping - Orthopedic or Neurologic?

Limping is often orthopedic in origin however in some situations limping can be of neurologic origin. Nerve root signature (NRS) sign is observed clinically as a non-weightbearing flexion of one limb, during standing, which may also appear like limping when gaiting. The suspected causes for NRS include vascular compression, inflammation or compression of a nerve root. This is most commonly noted in the thoracic limbs but has been reported in the pelvic limbs also.
In a recent study, a group from NCSU evaluated dogs with cervical disc herniations to see what criteria were present when they had signs of a NRS. This study included 47 dogs. Not surprisingly, all 47 had signs of cervical hyperesthesia with signs like ataxia (n=14), intermittent lameness (n=7), tetraparesis (n=2) and tetraplegia (n=1) being observed less frequently. I personally am not sure how you can identify a dog with a root signature sign if they’re plegic…but apparently, they did! Interestingly (to me) the site of disc herniation was C2-C5 in 20 dogs (43%) and C5-T1 in the other 27 dogs (57%). The nerve roots are supposed to arise from the C6-T2 region which is why it would make the most sense that a NRS sign should involve those nerve roots. Why did the C2-C5 region have NRS signs? Perhaps there was tethering of the nerve roots from "tugging" secondary to a cranially located disc. Perhaps anatomically they had a neve root arise more cranial than typical.
Spinal cord compression was mild in the majority of cases but remember it takes a TON of disc material in the cervical spinal cord to result in compression. Mild spinal cord compression is often surgical because the canal is much more voluminous around the smaller spinal cord (which is different from the thoracolumbar spine). Therefore the canal can contain loads of disc material yet the spinal cord has room to scootch over away from the disc, thus resulting in mild compression. Disc material was almost 3x more likely to be located laterally, within the spinal canal, than medially. Additionally, dogs were 2x more likely to have disc material compressing a nerve root compared to dogs without NRS. The last interesting finding is that 75% of the dogs in this study were over 7 years old. Typical chondrodystrophic disc degeneration with resulting herniation occurs in ages 3-7 year old. Is there a relationship between age, site of disc herniation and NRS or was this coincidental? I’m not sure but felt it was worth of comment.
 
Take away message:
Thoracic limb limping is often orthopedic in origin, however NRS should be considered for cases in which orthopedic disease is not identified. Nerve root signature sign secondary to a cervical disc herniation is more likely to be lateralized and therefore referral for surgical correction is strongly recommended to alleviate the compression to the nerve root.
 
Thanks for reading! Are we through deep winter? I’m not sure but I sure hope you’re staying warm! Please reach out with any questions about root signature sign or other neurologic cases. Have a great week!

Tick Paralysis and Dogs

The ticks are still here but owners may have stopped applying topical treatments. So fall is the time to be on the look out for Tick Paralyses (okay, really anytime but now isn't a BAD time to be aware)!

What causes Tick Paralysis?

Salivary transfer from a Dermacentor (in America) and Ixodes (in Australia, for my Australian readers) will result in neuromuscular blockade. How it actually works is really pretty ingenious. (Skip this next part if you're in a hurry.) At the presynaptic terminal, acetylcholine packets must be released into the neuromuscular junction so they can then bind to the post synaptic (muscle) membrane receptors. The acetylcholine binds to the presynaptic membrane using specific proteins as well as calcium. The saliva from one of the aforementioned types of ticks will interfere with acetylcholine release at the presynaptic terminal by binding calcium. Amazing, really.  

What are the common clinical signs?

If you cannot release acetylcholine from the presynaptic membrane at the neuromuscular junction, what can you do?  Exactly...nothing. 

Therefore clinical signs are an ascending pelvic to thoracic limb flaccid paralysis. No reflexes, no motor, no paw replacement, nada. These signs begin 5-9 days after exposure to the tick saliva. Cranial nerves are RARELY affected. This is important because botulism more commonly affects cranial nerves and this can be one way to try to differentiate between these two diseases. 

How do you make the diagnosis?

1. Find the tick.
2. Remove the tick.
2.5 (Apply Frontline/Bravecto/other)
3. Clinical improvement should begin 24-48 hours after tick removal.
No specific testing is available to confirm the diagnosis. 

I once had to find a tick on an Old English Sheepdog waaaay back in the year 2000. Topical tick treatment wasn't as prevalent then as it is now, so our solution was to shave the dog. We found the tick between the dog's toes. (Insert eye rolling here!!) In 2023, I suggest applying Frontline/Bravecto (your choice of topical flea treatment) first then perform a non-invasive tick hunt and monitoring for clinical improvement. If ineffective after 48 hours you can either commence a thorough tick hunt, or search for other causes of flaccid paralysis. (Or, call me for a neurology consultation!)

How do you manage patients flaccid paralysis?

Flaccid paralysis means that the animal does not have reflexes, or voluntary motor. As such, these animals may be at risk of respiratory failure due to loss of intercostal muscle function. Frequent CO2 monitoring, respiratory watch and ventilatory support if needed can be very important in the early stages of disease. Due to the rapid recovery common with tick paralysis, most patients do not need long-term intensive nursing care or physical therapy. 

Thank you for reading!  I appreciate you, and all that you do for your patients. Please note that I'm currently in Australia and will have delays in email response and NO telephone service. You can message me through FB if you want to but otherwise email is best. Thanks!!

Immune-mediated Polyneuropathy in cats

Riddle me this: a 10 month old cat is brought into your exam room by a very concerned owner. They report that the cat has had a rapid, progressive weakness develop over the past 2 weeks. Being the astute veterinarian that you are, you notice that the cat takes 3-4 steps and then sits. There doesn't appear to be any ataxia...just paresis (weakness). 

Neurologic examination:
Mentation: BAR
Cranial nerves: all normal (about 11% of cats will have facial nerve paralysis with this disease)
Gait: Ambulatory tetraparesis, worse in the pelvic limbs
Reflexes: reduced withdrawal all limbs, absent patellar reflexes bilaterally. 
Postural reactions: reduced to absent tactile placing in both pelvic limbs, reduced tactile placing in both thoracic limbs. 
Palpation: non-painful

The remainder of the physical examination is unremarkable.

What is the neuroanatomic lesion localization?

Start at the very beginning. Are there any signs of seizures, mentation changes or cranial nerve deficits? No. Therefore this cannot be intracranial lesion localization. We have all four limbs affected therefore if this is a spinal neuroanatomic lesion localization it must be cranial to the front legs. This means C1-C5 or C6-T2 myelopathy. (If the lesion was T3-L3 or L4-S3, the thoracic limbs should be normal.) To narrow it down between C1-C5 or C6-T2, we look at reflexes. Reflexes are reduced in the thoracic limbs therefore this would suggest a C6-T2 myelopathy. BUT WAIT!! The reflexes in the pelvic limb are also reduced to absent and that cannot happen with a C6-T2 spinal cord lesion. The reflexes in the pelvic limbs should be normal with a C6-T2 spinal cord lesion. Is this a multifocal lesion, affecting two spinal cord segements (C6-T2 and L4-S3)? Although possible, you would expect a proprioceptive ataxia with a spinal cord lesion therefore this is very unlikely to be a spinal cord lesion at all, even a multifocal spinal cord lesion. There, we must assume this is not spinal cord or intracranial lesion. What does that leave us? Neuromuscular disease, that's right! Your options are: 1) peripheral nerve, 2) neuromuscular junction or 3) muscle. Animals with muscle disease should have normal reflexes (and do, except with myasthenia gravis), so it isn't that. This is either a neuromuscular or peripheral neuropathy localization. 

Our differential diagnosis would include diseases such as: toxoplasma or fungal neuropathy, myasthenia gravis (yes, I know this localizes to the muscle but clinical signs look like a junctionopathy at times!), and immune mediated neuropathy. 

Diagnostic testing for this patient

CBC, serum biochemistry (including CK!) is normal. Toxoplasma testing was negative, as is the myasthenia gravis titer. Occasionally we will see an elevated CSF WBC or protein count with this mystery disease, but it isn't common. 

Muscle and nerve biopsy results

Diffuse variability in muscle fiber size is expected on biopsy. Nerves are almost all missing from the muscle biopsy sections. The nerve biopsy is markedly abnormal, with inflammatory cells infiltrating the axon, nodes of Ranvier and Schwann cells. 

Diagnosis: Immune mediated polyneuropathy!

This is a very interesting disease for many reasons but most notably, most cats can achieve a complete recovery without any treatment at all. In a recent study (see below), 10/11 cats that received no treatment obtained full recovery with a median time of 4 weeks. Nine of 12 cats that received glucocorticoids and 18/20 cats that received L-carnitine supplementation recovered as well. Relapses are reported and can occur months or years after resolution of signs. Overall, all except 1 cat improved regardless of treatment in this study. This same study found a predominance in males but did not find a breed association. 

So there you go! A self resolving, relapsing remitting polyneuropathy of young cats. 

Article: DOI: 10.1111/jvim.16701

I hope you have a great week and look forward to working with you soon!

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. 

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!

Flaccid Paralysis: Diagnosis and Treatment

Last week we discussed a case of flaccid paralysis that was localized to the neuromuscular system, specifically either neuromuscular junction or peripheral nerve. This week, we'll talk briefly about pursuit of diagnostic testing and treatment for these cases.

Diagnostic Testing
This group of diseases is a diagnostic challenge. In academic, or specialty clinics, electrodiagnostic testing may be recommended to look for hallmark changes amongst these group of diseases. Aside from not being readily available, electrodiagnostic testing is also imprecise when attempting to differentiate between this group of diseases. So what do we do? We attempt to differentiate based on history and physical exam findings. For example, animals with polyradiculoneuritis (Coonhound paralysis) are often hyperesthetic with normal bladder function and may, or may not have a history of contact with wildlife (Racoon). By contrast, those with botulism often have urinary retention, reduced mentation and mydriasis. Dogs with tick paralysis rarely have cranial nerve deficits and may have the mildest signs of the group. Coral snake bite results in rapid death (and is only found in the southern states). Organophosphate toxicity is frequently discovered when reviewing the history. Signs of SLUD (see below) or a history of exposure to organophosphate containing products can help guide this diagnosis. Blood cholinesterase levels can be measured (I've never done it) but they aren't reliable once the neurologic signs are apparent.

Treatment Options
Clinical suspicion can only get us so far. At some point we start treatment for the most likely cause. I will often recommend application of a tick product (example: frontline), even if a "tick check" is negative for the patient. Tick paralysis typically begins to improve within 24 hours after application of the product, further increasing your suspicion of the cause.

Polyradiculoneuropathy can progress to respiratory failure so referral for ventilator support is critical for dogs exhibiting reduced cutaneous trunci reflexes. Evaluation of CO2 levels can help you detect if the animal is not ventilating appropriately. No specific treatment is available for polyradiculoneuropathy. Supportive care with assistance to eat, drink and nursing care to maintain cleanliness are critical during the recovery period. These animals can void voluntarily, however they cannot move away from soiled bedding therefore bedsores are a high risk for this patient population. Physical rehabilitation is helpful for recovery so please get these dogs to PT as soon as you can! Recovery may take 4 to 6 months in dogs with severe disease, or 1-3 months in dogs with mild cases.

Botulism is diagnosed with detection of the toxin in serum, feces or gastric contents. This is extremely hard to do, and rarely is a confirmed diagnosis made. Supportive care with fluid support, urinary bladder catheterization, and management of secondary infections may help reduce the risk of death however Botulism is commonly fatal. An older report (Bruchim Y, The Vet Record 2006) describes the rare successful treatment of a mixed breed dog with botulism utilizing supportive care measures.

My experience with coral snake envenomation is limited to only a few cases during my residency at the University of Florida. Each case had a fatal outcome so I don't have a lot of treatment recommendations or supportive care ideas. If you live in the southern US - reach out to your local neurologist for additional help if you encounter a case.

Organophosphate toxicity results in paralysis from blockade of the acetylcholinesterase in the body, thus causing prolonged exposure to AcH at the receptor. This results in acute SLUD (salivation, lacrimation, urination, and defecation) followed by muscle weakness. No specific treatment is available. Atropine does not help once the SLUD has passed and the dog has progressed into the neuromuscular weakness signs. Supportive care, again, is the way to go. This may include ventilator support, along with nursing care and nutritional support. Signs may improve within 7 days after onset, but death is common. (Hopper, K, et al. JVECC 2002)

Whew! These cases are tough! Sometimes we "treat for the treatable" causes because that is all we can do. Keep up the good work and thanks for including me in your case management. I love working with you on the "easy" and the "hard" stuff!

Flaccid Paralysis in the Midwest

It's Tuesday afternoon and you have an emergency case coming that is reported to be unable to walk. Your staff tells you that you will be seeing a 5 year old Labrador that was found unable to walk in the back legs today. You square your shoulders and remind yourself of the common neuroanatomic lesion localizations for the spinal cord, and enter the room. After performing a thorough neurologic exam (self high five!) you conclude the following findings:

Mentation: BAR
Cranial nerves: reduced blink reflex bilaterally with normal corneal reflex, menace response, PLR, physiologic nystagmus and gag reflex.
Gait: Non-ambulatory tetraparesis
Reflexes: absent withdrawal reflex in both pelvic limbs, absent patellar reflexes bilaterally, absent panniculus reflex bilaterally, and reduced withdrawal reflexes more right thoracic limb than left, but both affected.
Postural reactions: When supported, paw replacement is absent in all four limbs
Palpation: non-painful, normal cervical range of motion

You make a hasty exit from the room and search for the number to your closest neurologist. Just kidding! You take a deep breath and realize that due to the multiple reduced reflexes in multiple limbs and cranial nerves, this must be neuromuscular, not spinal and not brain. Great job! What does neuromuscular actually mean?

Neuromuscular Neuroanatomic Lesion Localization:
Neuropathy - reflexes are reduced to absent, paresis without ataxia.
Junctionopathy - reflexes are typically absent however Myasthenia gravis is a junctionopathy and reflexes can be normal for this disease. Again, paresis or plegia without ataxia.
Myopathy - reflexes are normal, dogs are just paretic and are not ataxia

This dog could be a neuropathy or a junctionopathy.

What are my top 5 differentials for a dog with acute, progressive, junctionopathy?
1. Tick paralysis
2. Polyradiculoneuritis (Coonhound paralysis)
3. Botulism
4. Coral snake envenomation (not common in the Midwest)
5. Organophosphate/carbamate intoxication

Stay tuned for next week's TidBit Tuesday to discuss how we might diagnose and manage these unique cases!

Thanks for reading - have a great week and stay safe.

The Weak Lab

Here is the scene: You're evaluating a 10 year old MC Labrador retriever for a 6 month history of progressive difficulty walking. Signs were first noted in the pelvic limbs but have recently been noted in the thoracic limns. As an astute vet, you also discover that the dog has become hoarse, too. (Nice job!)

Physical examination: Unremarkable other that OA in the stifles from prior CCL injury and surgery .

Neurologic examination:
Mentation: BAR
Cranial nerves: Hoarse voice and harsh breathing consistent with laryngeal paralysis. Remaining cranial nerve examination normal.
Gait: ambulatory, slapping limb gait when walking, especially in the pelvic limbs. The dog appears to walk like he is wearing clown shoes.
Postural reactions: Absent paw replacement testing all four limbs

Reflexes: Absent femoral reflex (bilateral), reduced gastroc reflexes (bilateral), reduced distal withdrawal of all four limbs but most notable distal to the hock bilaterally, unable to obtain bicep reflexes (bilateral). Intact perineal, and reduced (but present) C. trunci throughout the entire TL region.
Palpation: Non painful spinal palpation, normal cervical ROM

Holy cow! What is this? (You might be wondering) This neurologic exam is all over the place!! I need help. (It's okay to stop here and call me or setup a consult.) However, since we're on a learning track today let's talk though this one together. I am willing to bet you can get this.

How to lesion localize this case if you lived inside of my brain:

1. First, we don't see any evidence of forebrain or brainstem disease, correct? (No CN deficits, no seizures, no mentation changes.) Okay, cross that off.

2. Secondly, all four limbs are involved. This cannot be T3-L3, or L4-S3 because ONLY the pelvic limbs would be affected. (See, we're getting somewhere!) Cross those off.

3. This leaves us C1-C5 or C6-T2 myelopathy, if this is spinal in origin. You might be tempted to say C6-T2 myelopathy because of the reflex deficits in the thoracic limbs but remember that we have reflex deficits in all four limbs and that just isn't possible with a C6-T2 myelopathy. You must have a lesion in the spinal cord plexus (C6-T2, L4-S3), or the nerve, or the neuromuscular junction to have a reflex deficit. Cross off C1-C5, and C6-T2.
   

4. Okay, big breath. This is NOT spinal cord in origin. It cannot be. It doesn't line up! We have ourselves a neuromuscular disease

What to do next, if you suspect neuromuscular disease

1. Neuropathy – reduced reflexes in multiple limbs, and/or limbs and head. Postural reactions may be reduced or absent. Pain is not noted on palpation. NO ataxia!

2. Junctionopathy – absent reflexes, non-ambulatory paresis or exercise induced non-ambulatory paresis. Depending on the severity, these animals may have a range reduced to absent postural reactions. (Myasthenia gravis is the exception. It is a junctionopathy but acts like a myopathy.)

3. Myopathy – Classically, these animals have a normal neurologic examination. (Think muscle disease, not neurologic disease) They are paretic (ranging from poorly ambulatory to ambulatory with fatigue) without any postural deficits or reflex deficits. Muscle pain, stiffness and pain on palpation may fool you into thinking they have spinal pain.

This case fits with a neuropathy, doesn't it? In fact, this is an example of a neuropathy. This dog has a neurodegenerative neuropathy common in Labrador retrievers. It is suspected to be genetic. The diagnosis is confirmed with muscle and nerve biopsy. (Yes, I can do these for you.)

Sadly, we do not have treatment available to reverse or slow down progression therefore treatment is supportive. Slings when needed, good solid footing such as rugs/carpet or yoga mats, and physical therapy are the mainstay of treatment. Supportive care with acupuncture has also been beneficial for some dogs.

Thanks for reading! Have a wonderful week and stay warm! I will be closed on January 28-29th. I appreciate your patience and look forward to connecting with you on Monday January 31st with any cases or questions you may have.

Brachial Plexus Injury and Recovery

Brachial Plexus Injury and Recovery

Nerve injury can take 3 different forms, from least to most severe:
1) Neurapraxia: transient function loss (ex: conduction block) with no loss of nerve anatomy.
2) Axonotmesis: disruption of axons with some (mild) degree of myelin loss. Importantly the surrounding perineurium and epineurium are intact.
3) Neurotmesis: complete rupture of the nerve (axon, myelin and all surrounding structures).This injury does not lend itself well to recovery.
**Important, but trivial sounding, note: Nerve root avulsion is irreversible.

A recent study evaluated traumatic nerve injury and outlined their findings. The most clinically applicable key points are listed below:

• 226 animals were included (175 dogs, 51 cats)

• 46% were injured before age 2

• Horner's syndrome was seen in 68 animals (42%of dogs and 38% of cats) with miosis ipsilateral to the affected thoracic limb. Note: It should always be ipsilateral unless there is spinal cord damage.

• Cutaneous trunci reflex (which has it's motor origin between C8-T2) was lost in 81% of dogs, again ipsilateral to the affected limb. This reflex doesn't count in cats. :)

Prognostic factors in this study were largely related to electrodiagnostic studies, which are not clinically useful markers in practice. (Unless you have access to electrodiagnostic testing...which I don't, anymore!) That said, we know that animals with neurotmesis do not recover and prior studies have identified that animals with axonotmesis can recover but it may take awhile. Nerves may regrow 1 inch per month for a total of 8 inches. Therefore distal injuries resulting in axonotmesis may result in some functional recovery of the limb.
In the study referenced below, the only important clinical prognostic indicator from this study was the absence of cutaneous trunci reflex. When, absent, it was linked to a lesser chance of recovery, but no statistical analysis was performed to assess this trend. This study also reinforced the finding that electrodiagnostic testing is a valuable testing tool for providing a prognosis for dogs and cats following brachial plexus injury.

Do you have a patient with a traumatic limb injury with possible neurologic involvement? A neurologic examination may be able to better identify chances of recovery and direct treatment towards appropriate physical therapy, acupuncture and other management during the recovery phase. Reach out if I can help!

Have a great week and stay warm in this chilly turn towards fall!

Referenced article: https://doi.org/10.1111/jvim.16254

Hypothyroidism and Neuropathies

Etiology: The peripheral nerve is the most common target in the neurologic system for hypothyroidism. What causes a peripheral neuropathy due to hypothyroidism? I'm glad you asked....

1) accumulation of mucinous deposits resulting in nerve entrapment
2) demyelination secondary to Schwann cell defect
3) vascular nerve damage secondary to hypothyroid induced dysfunction of BBB
4) disruption of axonal transport

Signalment:

• Typically older dogs, however congenital disease does (rarely) happen. NOTE: dogs are not always overweight, heat-seeking or have flaky-hair coats with peripheral neuropathy signs.
  
  

Clinical signs:

• A polyneuropathy is most common. This results in paresis without ataxia and reduced to absent peripheral spinal reflexes. Signs may be initially mild.

• Cranial nerve deficits such as facial nerve paralysis (VII), vestibular dysfunction (VIII), or laryngeal paralysis (X).

• Hypothyroidism may also cause a myopathy and/or megaesophagus.

Diagnostic tests:

• T4 is a good first step. If abnormal, a full panel is recommended.

Treatment options:

• You guessed it...supplementation!

Prognosis:

• The neuropathy is likely to improve a little or a lot, after several months with therapy if the axonal degeneration is not too severe.

• Cranial nerve deficits may persist even with appropriate treatment.

Frequency:

• Common in older dogs! (And recently seen in one cat with vestibular signs. This job always keeps me on my toes, that's for sure!)

This is Neurology Month for the WVMA. If you haven't seen already, there are 4 virtual talks available to WVMA members, and non-members, for CE credit. I do not receive any payment for promoting this but, I am one of the speakers!

Have a great week, and keep those consults coming. Consults are available Monday-Saturday at variable times so please reach out if I can help you with a case.

Neospora caninum: Update!

Medical Review: Neospora Myositis

You might be wondering why on Earth I'm talking about Neospora as a small animal vet. (Neospora causes abortion in cattle!) It infects dogs too!! Some of you have seen some positive cases with me throughout 2020 so, I thought it was worthwhile doing a mini-review so we could all brush up on it together.

Etiology: Toxoplasma gondii and Neospora caninum may cause myositis, peripheral neuritis or CNS meningoencephalitis.

Signalment:

Breed: any
Age: may be acquired in utero leading to signs at a very young age (months), or by consuming raw or under cooked meat causing signs at any age. **Adult onset is what I see most commonly. However, the dog pictured above was a puppy that presumably acquired it in utero.

Clinical signs: Stiff gait, muscle pain (myalgia), muscle atrophy. Note: Muscle atrophy can be anywhere including the muscles of mastication. I have been tricked into thinking a dog has MMM when in actuality it had Neospora myositis causing unilateral muscle atrophy in the masticatory muscles.

Diagnostic tests: IFA > 1:200 for Neospora caninum is consistent with an infection, however documentation with a repeated titer is recommended as a confirmatory test. Muscle biopsy showing the encysted organism is definitive but obviously the most invasive route.

Treatment options: Sulfadimethoxazine/ormetoprim (15 mg/kg PO q12h) or clindamycin (10 mg/kg PO q12h) twice daily is recommended for 4-6 weeks, possibly longer. Be aware that sulfa antibiotics can cause idiosyncratic myopathic drug reactions too!

Prognosis: Good, if treatment is started before severe muscle atrophy or fibrosis is present. Prognosis is poor if clinical signs are severe, or chronic.

Frequency: Uncommon, but not unheard of!

Voila! TidBit Tuesday-style update on Neospora caninum. 😊

Final question: When do I run the IFA? Answer: Any dog with a history of muscle pain, muscle atrophy (not explained by neuropathic disease) or an elevated CPK should have a Neospora titer performed. This disease is sneaky so I err on the side of caution and suggest running the test rather than getting caught unawares.

Be safe, be strong and keep those referrals coming!
Heads up for those of you in my referral area: I will be closed Thursday January 28th to celebrate my youngest kiddo turning 5 years old. My, how time flies! I apologize for any inconvenience this may cause and look forward to consulting with you on another day!

Tick Paralysis and Dogs

Tick Paralysis and Dogs

The ticks are still here but owners may have stopped applying topical treatments. So fall is the time to be on the look out for Tick Paralyses (okay, really anytime but now isn't a BAD time to be aware)!

What causes Tick Paralysis?

Salivary transfer from a Dermacentor (in America) and Ixodes (in Australia, for my Australian readers) will result in neuromuscular blockade. How it actually works is really pretty ingenious. (Skip this next part if you're in a hurry.) At the presynaptic terminal, acetylcholine packets must be released into the neuromuscular junction so they can then bind to the post synaptic (muscle) membrane receptors. The acetylcholine binds to the presynaptic membrane using specific proteins as well as calcium. The saliva from one of the aforementioned types of ticks will interfere with acetylcholine release at the presynaptic terminal by binding calcium. Amazing, really.  

What are the common clinical signs?

If you cannot release acetylcholine from the presynaptic membrane at the neuromuscular junction, what can you do? 

Exactly, nothing. 

Therefore clinical signs are an ascending pelvic to thoracic limb flaccid paralysis. No reflexes, no motor, no paw replacement, nada. These signs begin 5-9 days after exposure to the tick saliva. Cranial nerves are RARELY affected. This is important because botulism more commonly affects cranial nerves and this can be one way to try to differentiate between these two diseases. 

How do you make the diagnosis?

1. Find the tick.
2. Remove the tick.
2.5 (Apply Frontline/Bravecto/other)
3. Clinical improvement should begin 24-48 hours after tick removal.
No specific testing is available to confirm the diagnosis. 

I once had to find a tick on an Old English Sheepdog waaaay back in the year 2000. Topical tick treatment wasn't as prevalent then as it is now, so our solution was to shave the dog. We found the tick between the dog's toes. (Insert eye rolling here!!) In 2020, I suggest applying Frontline/Bravecto (your choice of topical flea treatment) first then perform a non-invasive tick hunt and monitoring for clinical improvement. If ineffective after 48 hours you can either commence a thorough tick hunt, or search for other causes of flaccid paralysis. (Or, call me for a neurology consultation!)

How do you manage patients flaccid paralysis?

Flaccid paralysis means that the animal does not have reflexes, or voluntary motor. As such, these animals may be at risk of respiratory failure due to loss of intercostal muscle function. Therefore CO2 monitoring, respiratory watch and ventilatory support if needed can be very important in the early stages of disease. Due to the rapid recovery, most patients do not need long-term intensive nursing care or physical therapy. 

I hope you are doing well and staying safe. I appreciate what you do to help clients and their pets. Let me know how I can help you manage your patients with neurologic disease.

On site consultation is available Monday through Saturday at variable times throughout the week. Email consults are completed in evenings. 

Have a good week!