Diffuse Lower Motor Neuron Dysfunction in Dogs

You have asked…A canine patient presented with sudden-onset pelvic limb weakness that rapidly progressed to inability to walk. Segmental reflexes were absent in all limbs. What differential diagnoses should be considered?

The expert says…A patient presenting with these signs may have a diffuse lower motor neuron (LMN) disorder (ie, diffuse neuromuscular disease) based on the absence of myotatic and withdrawal reflexes in all limbs.

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Diffuse LMN signs may result from generalized muscle dysfunction; neuromuscular junction disorders; or disease of the peripheral motor nerves, ventral (motor) nerve roots, or motor neurons within the spinal cord. Diffuse spinal cord disease is also possible in these patients but is less common than diffuse neuromuscular disease. Although ataxia and paraspinal hyperesthesia are occasionally observed in patients with diffuse neuromuscular disease, both signs are more likely with spinal cord dysfunction than with a generalized peripheral LMN disorder. This distinction can help practitioners differentiate diffuse spinal cord disease from neuromuscular disease.

The differential list for LMN dysfunction is varied (see LMN Dysfunction: Differentials & Considerations), and regional risk conditions (eg, coral snake envenomation) should be considered, but 4 of the most common causes of acute diffuse LMN dysfunction are acute idiopathic polyradiculoneuritis or coonhound paralysis,¹ tick paralysis, botulism, and fulminant (acute) myasthenia gravis.

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LMN Dysfunction: Differentials & Considerations

• Acute polyradiculoneuritis

• Antibacterial-associated neurotransmission disorder

• Degenerative myopathy

• Distal denervating disease

• Envenomation (eg, coral snake)

• Fulminant myasthenia gravis

• Ionophore toxicity (eg, monensin)

• Lead toxicity

• Metabolic disorder (eg, Addison’s disease [hypoadrenocorticism], diabetes mellitus)

• Neospora caninum and Toxoplasma gondii parasitism

• Organophosphate and carbamate toxicity

• Polymyositis

• Tick paralysis

Acute Diffuse LMN Dysfunction: 4 Common Differential Diagnoses

1. Acute idiopathic polyradiculoneuritis or coonhound paralysis2. Tick paralysis3. Botulism4. Fulminant (acute) myasthenia gravis

Related Article: Paralysis by Parasite

1. Acute Idiopathic Polyradiculoneuritis or Coonhound ParalysisAcute idiopathic polyradiculoneuritis is an inflammatory disorder that primarily affects the axons and myelin of the ventral roots and shares the same clinical and pathologic features of Guillain-Barré syndrome in humans.² The inciting cause is unknown, but theories include recent illness or vaccination, immune-mediated disease, and viral infection. A recent retrospective study demonstrated that dogs with this condition were more likely to have positive serum IgG titers for Toxoplasma gondii than were dogs not affected by this condition, suggesting that T gondii may be an inciting trigger.¹

Coonhound paralysis appears to be an identical clinical disease in dogs that have been exposed to raccoon bites or scratches 7 to 10 days before onset of clinical signs. Salivary antigen may trigger the condition. In both diseases, the history typically reflects sudden onset of pelvic limb weakness that progresses to nonambulatory tetraparesis within 48 to 72 hours.

Neurologic examination (See Table) may reveal flaccid tetraparesis or tetraplegia, decreased to absent myotatic reflexes, and decreased to absent withdrawal. Loss of voice or change in bark is common, and some patients have facial weakness. Typically, these patients do not become incontinent, and their sensory function remains intact; some may appear hyperesthetic.

DiagnosisDiagnosis is based on history, potential exposure to raccoons, and neurologic examination findings. Electrodiagnostics can be helpful, but abnormalities in electrical activity do not develop until 5 to 7 days after onset of signs. Abnormal spontaneous electrical activity is frequently detected on electromyography, and motor nerve compound muscle action potentials and nerve conduction velocity are often diminished. A special type of nerve conduction study (ie, F wave) that assesses transmission through the ventral roots may be abnormal, suggesting disease of the ventral roots. Cerebrospinal fluid often demonstrates an elevated protein level.²

TreatmentTreatment is centered on intensive nursing care (eg, hydration, nutritional support, prevention of pressure sores, recumbent patient care) and physical rehabilitation. Most patients do not have urinary or fecal incontinence, but an indwelling urinary catheter should be considered to lower risk for urine scald. Although this disease has inflammatory attributes, glucocorticoids have not been shown to shorten disease duration or improve degree of recovery; furthermore, glucocorticoids can worsen the weakness. In human medicine, plasma exchange (plasmapheresis) and high-dose intravenous immunoglobulin (IVIG) therapy are commonly used for patients with Guillain-Barré syndrome. Data are limited as to whether IVIG therapy shortens the duration of signs or improves degree of recovery in dogs.³ In addition, plasmapheresis is available in few veterinary practices, and IVIG can be difficult to acquire; both can be cost prohibitive.

The most important monitoring parameter for these patients is ventilation, as signs can progress over 5 to 7 days; some patients develop respiratory muscle weakness from involvement of the phrenic nerve and intercostal nerves. These patients may require mechanical ventilation, but most will eventually recover if they do not develop pneumonia or other complications.

The prognosis is good to excellent with intensive nursing care and physical rehabilitation; however, complete recovery may take several weeks to months. Clients should be instructed to avoid exposure to raccoons or other factors that may have triggered the clinical signs, as survival does not confer immunity.

2. Tick ParalysisTick paralysis is characterized by a flaccid, rapidly ascending LMN paralysis in dogs following exposure to salivary neurotoxin released by adult ticks. Dermacentor variabilis (American dog tick, common wood tick) and D andersoni (Rocky Mountain wood tick) are most commonly implicated in the United States. Affected dogs typically display signs 5 to 9 days after tick attachment and present with paraparesis that rapidly progresses to tetraparesis within 12 to 72 hours of onset of signs.

DiagnosisDiagnosis is based on removing an engorged tick, followed by rapid resolution of signs. Failure to find a tick does not rule out tick paralysis (eg, the tick may have dropped off). The patient should be treated with an acaricide (tick dip) if available. If an acaricide is not readily available, the patient should be shaved completely in search for ticks. Manually locating ticks in dogs with long hair coats is unreliable. Inner pinnae, under the tail, and perivulvar and interdigital regions (ie, locations where ticks are frequently encountered) should be closely scrutinized. Investigation should not stop after an engorged tick is found; there is often more than one tick on an affected patient.

TreatmentImprovement is often noted within hours of tick removal, and full recovery can occur within 2 to 3 days. Spot-on tick treatment should not be the sole measure, as spot-on treatment can require 36 to 48 hours to take effect, during which time respiratory paralysis or aspiration pneumonia may develop. There is little value in performing tick serology for suspected tick paralysis. A positive test result simply suggests tick exposure at some point in the past (potentially months to years) that led to tick-borne infection, not necessarily the same tick causing the current signs. If the test proves negative, the patient could still have tick paralysis.

3. BotulismBotulism is caused by ingestion of a preformed neurotoxin produced by Clostridium botulinum. This organism produces multiple exotoxins, but type C neurotoxin has been implicated most commonly in canine botulism. The toxin is most likely ingested through contaminated carrion or uncooked, spoiled food. In rare cases, the organism produces the exotoxin after colonization of the GI tract. After absorption from the upper GI tract, the neurotoxin enters the circulatory system and is internalized into the nerve terminal of presynaptic neurons, where it binds to synaptic vesicle fusion proteins (syntaxin, synaptobrevin). This prevents fusion of neurotransmitter vesicles to the presynaptic membrane, thereby blocking release of acetylcholine (ACh) at both the neuromuscular junction and cholinergic synapses in the autonomic nervous system.

Onset of clinical signs occurs within 12 hours of ingestion. Clinical signs often appear as progressive weakness to flaccid paralysis, starting in the pelvic limbs and rapidly progressing to the thoracic limbs. Pain perception in the limbs remains intact. In severe cases, respiratory paralysis can lead to death. Unlike the other LMN diseases described in this article, cranial nerve deficits are common, including facial nerve paralysis, decreased gag reflex, decreased jaw tone, and megaesophagus. Autonomic nervous system signs also are common, including altered heart rate, dilated pupils with decreased pupillary light reflex, keratoconjunctivitis sicca, urine retention, and constipation.

DiagnosisPresumptive diagnosis is based on evaluation of signs and potential exposure. Definitive diagnosis requires identification of the neurotoxin in blood, feces, vomitus, or food. Electrodiagnostics can help distinguish botulism from other diseases.

TreatmentTreatment consists of routine nursing care, physical therapy, and bladder and bowel care. Type C antitoxin is difficult to obtain, must be given within the first few days (before the toxin has internalized into neurons), and has uncertain therapeutic benefit. Trivalent antitoxins (types A, B, and E) do not appear to be beneficial. Patients do not develop immunity, but repeat exposure is rare.

4. Fulminant (Acute) Myasthenia GravisThis uncommon form of acquired myasthenia gravis (MG; see Types of Myasthenia Gravis) can produce severe, rapidly progressive generalized muscle weakness. Acquired MG is caused by antibodies directed against the ACh receptor on skeletal muscle, resulting in decreased receptors available for ACh binding and subsequent muscle weakness.

Patients with fulminant MG often present as laterally recumbent nonambulatory tetraparetics. They may have normal to only mildly decreased myotatic spinal reflexes, whereas patients with the other 3 described disorders usually have markedly reduced reflexes. Aspiration pneumonia, a result of laryngeal and pharyngeal weakness, is common. These patients often appear systemically ill.

DiagnosisDefinitive diagnosis is based on demonstration of anti-ACh receptor antibodies in serum. Tensilon testing (edrophonium challenge) often yields a false-negative result because of the weakness severity; false-positive results are also possible, although a dramatic improvement in strength would be more common with MG than with other disorders. Thoracic radiographs should be examined for megaesophagus, aspiration pneumonia, or thymoma. Routine screening tests (eg, CBC, serum biochemistry profile, abdominal ultrasonography) are often normal but should be performed to search for an underlying cause and to rule out other causes of generalized weakness. Electrodiagnostic testing (ie, repetitive nerve stimulation or single-fiber electromyography) may support a diagnosis of MG.

TreatmentTreatment involves intensive care with anticholinesterase therapy (eg, oral pyridostigmine, injectable neostigmine), potentially immunosuppressive medications (used cautiously if aspiration pneumonia is present and with the knowledge that corticosteroids can cause additional neuromuscular weakness), IV fluids, and nutritional support. Plasmapheresis and/or IVIG therapy may help but are used infrequently because of cost and limited availability. This form of MG has a high mortality.

ACh = acetylcholine, IVIG = intravenous immunoglobulin, LMN = lower motor neuron, MG = myasthenia gravis

MARK TROXEL, DVM, DACVIM (Neurology), is staff neurologist and neurosurgeon at Massachusetts Veterinary Referral Hospital in Woburn. His publications include articles and book chapters. His interests include canine and feline brain tumors, vestibular dysfunction, and neurosurgery, topics on which he lectures nationally. Dr. Troxel completed a rotating internship, medicine specialty internship, and neurology residency at University of Pennsylvania. He earned his DVM from Iowa State University.

References

1. Seroprevalence of various infectious agents in dogs with suspected acute canine polyradiculoneuritis. Holt N, Murray M, Cuddon PA, Lappin MR. JVIM 25:261-266, 2011.2. Electrophysiologic assessment of acute polyradiculoneuropathy in dogs: Comparison with Guillain-Barré syndrome in people. Cuddon PA. JVIM 12:294-303, 1998.3. Clincal course of acute canine polyradiculoneuritis following treatment with human IV immunoglobin. Hirschvogel K, Jurina K, Steinberg TA, et al. JAAHA 48:299-309, 2012.

Suggested Reading

Acquired canine peripheral neuropathies. Cuddon PA. Vet Clin North Am Small Anim Pract 32:207-249, 2002.Myasthenia gravis and disorders of neuromuscular transmission. Shelton GD. Vet Clin North Am Small Anim Pract 32:189-206, 2002.Myasthenia gravis in dogs with an emphasis on treatment and critical care management. Khorzad R, Whelan M, Sisson A, Shelton GD. JVECC 21:193-208, 2011.