Lower Motor Neuron Disease

Chapter 101 Lower Motor Neuron Disease



Charles Vite, DVM, PhD, DACVIM (Neurology), Kersten Johnson, DVM



KEY POINTS



• The motor unit is comprised of the lower motor neuron (LMN), the neuromuscular junction (NMJ), and skeletal muscle fibers.

• Disease of the motor unit results in flaccidity, diminished segmental reflexes, and rapidly progressing muscle atrophy.

• In contrast, upper motor neuron (UMN) paresis or paralysis results in spasticity and exaggerated segmental reflexes.

• Clinical signs, clinicopathologic testing, and electrodiagnostic testing can be used to identify the location of the disease within the motor unit.

• Cranial or spinal neuropathies and local or diffuse myopathies result from neoplastic, degenerative, genetic, immune-mediated, metabolic, vascular, toxic, infectious, or idiopathic causes. Botulism, tick paralysis, acquired myasthenia gravis, or aminoglycoside intoxication may cause diffuse junctionopathies.


INTRODUCTION


The lower motor neuron (LMN) is comprised of the cell body (found in the brainstem or spinal cord) and the axon that contributes to either the spinal or cranial nerves. The LMN terminates on skeletal muscle fibers at the neuromuscular junction (NMJ). The LMN, NMJ, and skeletal muscle fibers together make up the motor unit.1


The upper motor neuron (UMN) system originates in the cerebral cortex and brainstem, with axons contributing to the corticospinal, rubrospinal, reticulospinal, or vestibulospinal tracts. The UMN is confined to the central nervous system and terminates on the LMN. Strictly defined, the UMN is a premotor neuron because it results only in movement and muscle tone through its actions on the LMN.2


The paretic or paralyzed patient may have disease of the brain, spinal cord, nerve, NMJ, or skeletal muscle. The neurologic examination and its interpretation are the first and most important steps in localizing the lesion. The first question asked is whether the clinical signs result from dysfunction of the UMN system or of the motor unit. Disorders of the UMN system typically result in spasticity and exaggerated segmental reflexes. Disorders of the motor unit result in flaccidity, diminished segmental reflexes, and rapidly progressing muscle atrophy (over 1 to 2 weeks). This chapter will describe how to recognize diseases of the motor nerve (neuropathy), NMJ (junctionopathy), and muscle (myopathy), how to confirm an anatomic diagnosis, and how to treat specific disorders of the motor unit.



IDENTIFYING NEUROPATHIES, JUNCTIONOPATHIES, AND MYOPATHIES


Disease of the motor unit results in flaccid paresis or paralysis. A short-strided gait is apparent when appendicular muscles are involved. Postural reactions and segmental reflexes frequently are diminished. Muscle atrophy is common, although involvement of specific muscle groups may result in specific dysfunction including incontinence, dysphagia, dysphonia, regurgitation, and abnormal facial expressions. In order to generate a list of appropriate differential diagnoses, the location of the lesion (nerve, NMJ, muscle) must first be determined using information from the clinical examination, clinicopathologic tests, electrodiagnostic testing, and/or biopsy.



Clinical Signs


Some clinical signs are specific to involvement of the nerve, NMJ, or skeletal muscle. Because neuropathies may affect sensory neurons in addition to the LMN, proprioceptive deficits and diminished tactile or pain sensation may be recognized with neuropathies, but not with diseases of the NMJ or muscle. In some instances, it can be difficult to distinguish whether an animal does not correct a knuckled over paw due to inability to sense that it is in an abnormal position (diminished proprioception) or due to paresis. If one supports most of the animal’s weight and places the dorsal surface of the paw on the floor, a paretic dog may replace the foot promptly, but a dog with significant proprioceptive deficits will not. Additional clinical signs that may suggest the location of the lesion are muscle pain (found with some myopathies) and waxing and waning signs that frequently are made worse with exercise (found with some junctionopathies and myopathies but uncommon with neuropathies).



Clinicopathologic Testing


Serum enzyme activities specific to muscle may help to identify myopathic disease. Large increases in the serum concentrations of the enzymes creatine kinase, serum glutamic aspartate aminotransferase, and lactate dehydrogenase can indicate damage to muscle fibers. Increases in serum activities of these enzymes must be interpreted with caution because damage to muscle may also occur from recumbency and trauma associated with any cause of paresis.


Cerebrospinal fluid (CSF) analysis may be useful to identify neuropathic disease. Many neuropathies, particularly those involving the nerve roots (radiculopathies) due to degenerative, neoplastic, or inflammatory processes can result in elevations in CSF protein and pleocytosis. These elevations are not expected in most myopathies or junctionopathies.



Electrodiagnostic Testing


Electrodiagnostic testing that is useful for evaluating disease of the motor unit includes electromyography (EMG) and evoked response testing. Electromyography can detect electrical discharges of muscle fibers that are independent of neural control. Spontaneous electrical activity known as fibrillation potentials and positive sharp commonly are recorded from damaged (myopathy) or denervated muscle (neuropathy) but are rarely found in junctionopathies.


Nerve fibers may also be stimulated electrically to produce compound muscle action potentials (CMAPs). The amplitude and duration of these evoked potentials and the conduction velocity along the nerve can be used to identify the location of the lesion. Small-amplitude evoked responses are found in neuropathies where axonal dysfunction is present (axonal neuropathies), and they can also be found with some junctionopathies and myopathies. Repetitive nerve stimulation is useful for identifying junctionopathies because it often causes the evoked CMAPs to have decreasing amplitude in cases of myasthenia gravis and increasing amplitude in animals with tick paralysis and botulism. A prolonged duration of the CMAP and a significant decrease in nerve conduction velocity can occur in neuropathies where myelin dysfunction occurs (demyelination neuropathies).



Nerve and Muscle Biopsy


Nerve and muscle biopsies may be required when electrodiagnostic testing cannot be performed or when the results of these tests are inconclusive. Nerve biopsy may reveal degeneration or inflammation of the axon or myelin associated with the neuropathy. Muscle biopsy may reveal fiber-type grouping, group atrophy, degeneration, inflammation, or infiltration with fat and connective tissue. Fiber-type grouping, the clustering of either type I or type II muscle fibers, and group atrophy (atrophy of adjacent muscle fibers of similar type) can be seen in animals with neuropathies. Myopathies generally are characterized by fibers affected in a more random pattern with muscle necrosis, regeneration, and inflammation commonly found.2



DECISION MAKING


When an animal has signs consistent with disease of the motor unit, the clinician should first determine which nerve and muscle are affected, based on the clinical examination. If a neuropathy is suspected, the distribution of the neuropathy should be ascertained (cranial versus spinal nerves, mononeuropathy versus polyneuropathy, purely motor neuropathy versus concomitant sensory or autonomic neuropathy).3 The distribution should be determined in a similar fashion in animals with myopathies (localized versus generalized). A list of differential diagnoses can then be generated.


Next, the onset and course of the clinical signs should be considered. Acute disease may be due to metabolic, neoplastic, inflammatory, traumatic, toxic, and vascular causes, with bilaterally symmetric disease resulting more commonly from metabolic, inflammatory, and toxic causes and asymmetric disease resulting more commonly from neoplastic and traumatic causes.


Next, the possible association of the neurologic dysfunction with any past or present diseases should be considered. Hematologic, biochemical, and serologic testing, as well as imaging, may be performed.


Finally, electrodiagnostic testing, nerve biopsy, and muscle biopsy may be done to confirm the distribution of the disease and to determine the nature of the lesion.



CAUSES OF ACUTE NEUROPATHY, MYOPATHY, OR JUNCTIONOPATHY



Cranial Mononeuropathies



Trigeminal Nerve Sheath Tumor


The client frequently recognizes a rapid loss of muscle over one side of the head of the dog, even though the malignant peripheral nerve sheath tumor (MPNST) is slow growing. Unilateral temporal, masseter, pterygoid, and digastric muscle atrophy may occur, the mandible may be directed toward the side of the lesion, and a unilateral loss of facial sensation may occur if sensory fibers are involved. As the mass grows and compresses the brain, signs of brainstem dysfunction may occur with hemiparesis and vestibular system dysfunction being particularly common. Diagnosis generally is made by computed tomography (CT) or magnetic resonance imaging (MRI) of the head. Surgery and radiation therapy have been attempted and may slow the progression of signs.4



Trigeminal Neuritis


Dogs (common) and cats (rare) with trigeminal neuritis have an acute inability to close the mouth and difficulty eating and drinking due to bilateral paralysis of the mandibular muscles. Decreased sensation of the face, due to involvement of sensory nerve fibers, and Horner syndrome, due to presumed involvement of sympathetic fibers adjacent to the ophthalmic branch of the trigeminal nerve, may also occur. The diagnosis is made by ruling out musculoskeletal causes for a dropped jaw. Other differential diagnoses for mandibular paralysis are rabies encephalitis (the clinician should wear gloves and obtain a complete vaccination history), round cell neoplasia, and early polyneuritis.5 Treatment is supportive and the animal is fed by placing small meatball-shaped foods in the mouth with the head elevated. Recovery usually occurs in 2 to 4 weeks, although up to 9 weeks is described.



Facial Nerve Paralysis


Dogs and cats generally present because of an inability to lift the lip, excessive drooling, and an inability to move the ear or blink the eyelid. Unilateral (common) or bilateral (less common) paralysis may occur. Signs may be due to inflammatory, neoplastic, traumatic, and idiopathic causes.6 In the idiopathic form, which may be the most common, tear production is preserved and signs may resolve in weeks to months with no specific therapy. Facial nerve paralysis due to otitis media/interna is indistinguishable from the idiopathic form unless accompanied by Horner syndrome or evidence of ear disease identified by otic examination, brainstem auditory evoked response testing, or imaging.


Surgical (bulla osteotomy) or medical therapy (cephalosporins, amoxicillin-clavulanic acid, clindamycin, enrofloxacin) of the ear disease may lead to resolution of the paralysis. Trauma to the nerve may occur following total ear canal ablation and may or may not resolve with time. Lymphosarcoma may also cause unilateral facial nerve paralysis. In these cases, the facial nerve typically is affected intracranially, in which case the major petrosal nerve may also be affected, resulting in decreased tear production.7 Finally, facial nerve paralysis may be a clinical sign of a polyneuropathy.

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Sep 10, 2016 | Posted by in SMALL ANIMAL | Comments Off on Lower Motor Neuron Disease

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