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Motor
neuron disorders are characterized by steady, relentless, progressive
degeneration of corticospinal tracts, anterior horn cells, bulbar motor
nuclei, or a combination. Symptoms vary in severity and may include
muscle weakness and atrophy, fasciculations, emotional lability, and
respiratory muscle weakness. Diagnosis involves nerve conduction
velocity studies, electromyography, and exclusion of other disorders via
MRI and laboratory tests. Treatment is supportive.
Motor neuron disorders (MNDs) may involve the CNS as well as the peripheral nervous system. Usually, etiology is unknown. Nomenclature and symptoms vary according to the part of the motor system most affected. Myopathies have similar features but are disorders of the muscle membrane, contractile apparatus, or organelles (see Inherited Muscular Disorders: Congenital Myopathies).
MNDs can be classified as upper and lower; some disorders (eg, amyotrophic lateral sclerosis) have features of both. They are more common among men, most often during their 50s.
Symptoms and Signs
Upper MNDs (eg, primary lateral sclerosis) affect neurons of the motor cortex, which extend to the brain stem (corticobulbar tracts) or spinal cord (corticospinal tracts). Generally, symptoms consist of stiffness, clumsiness, and awkward movements, usually affecting first the mouth, throat, or both, then spreading to the limbs.
Lower MNDs affect the anterior horn cells or cranial nerve motor nuclei or their efferent axons to the skeletal muscles. In bulbar palsies, only the cranial nerve motor nuclei in the brain stem (bulbar nuclei) are affected. Patients usually present with facial weakness, dysphagia, and dysarthria. When anterior horn cells of spinal (not cranial) nerves are affected, as in spinal muscular atrophies (see Peripheral Nervous System and Motor Unit Disorders: Spinal Muscular Atrophies), symptoms usually include muscle weakness and atrophy, fasciculations (visible muscle twitches), and muscle cramps, initially in a hand, a foot, or the tongue. Poliomyelitis, an enteroviral infection that attacks anterior horn cells, and postpolio syndrome are also lower MNDs (see Enteroviruses: Poliomyelitis).
Physical findings help differentiate upper from lower MNDs (see Table 3: Peripheral Nervous System and Motor Unit Disorders: Distinguishing Upper From Lower Motor Neuron Lesions ) and weakness due to lower MNDs from that due to myopathy (see Table 4: Peripheral Nervous System and Motor Unit Disorders: Distinguishing the Cause of Muscle Weakness: Lower Motor Neuron Dysfunction vs Myopathy*).
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Table 3
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Distinguishing Upper From
Lower Motor Neuron Lesions
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Feature
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Upper Lesion
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Lower Lesion
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Reflexes
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Hyperactive
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Diminished or absent
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Atrophy
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Absent*
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Present
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Fasciculations
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Absent
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Present
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Tone
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Increased
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Decreased or absent
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*May appear with prolonged disuse of limbs.
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Table 4
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Distinguishing the Cause
of
Muscle Weakness: Lower Motor Neuron
Dysfunction vs Myopathy*
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Feature
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Lower Motor Neuron Dysfunction
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Myopathy*
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Distribution of weakness
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Distal
> proximal
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Proximal > distal
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Fasciculations
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May be present
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Absent
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Reflexes
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Diminished
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Often preserved
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Sensory symptoms and signs
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May be present
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Absent
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*Nerve function intact.
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> = more affected than.
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Amyotrophic
lateral sclerosis (ALS):
ALS (Lou Gehrig disease, Charcot's syndrome) is the most common MND.
Most patients present with random, asymmetric symptoms, consisting of cramps, weakness, and muscle atrophy of the hands (most commonly) or feet. Weakness progresses to the forearms, shoulders, and lower limbs. Fasciculations, spasticity, hyperactive deep tendon reflexes, extensor plantar reflexes, clumsiness, stiffness of movement, weight loss, fatigue, and difficulty controlling facial expression and tongue movements soon follow. Other symptoms include hoarseness, dysphagia, slurred speech, increased saliva production, and a tendency to choke on liquids. Late in the disorder, a pseudobulbar affect occurs, with inappropriate, involuntary, and uncontrollable excesses of laughter or crying. Sensory systems, consciousness, cognition, voluntary eye movements, sexual function, and urinary and anal sphincters are usually spared
Death is usually caused by failure of the respiratory muscles; 50% of patients die within 3 yr of onset, 20% live 5 yr, and 10% live 10 yr. Survival for > 30 yr is rare. In the bulbar variant, deterioration and death occur more rapidly.
Progressive
bulbar palsy:
The muscles innervated by cranial nerves and corticobulbar tracts are predominantly affected, causing progressive difficulty with chewing, swallowing, and talking; nasal voice; reduced gag reflex; fasciculations and weak movement of the facial muscles and tongue; and weak palatal movement. A pseudobulbar affect, with emotional lability may occur if the corticobulbar tract is affected. Commonly, the disorder spreads, affecting extrabulbar segments; then it is called bulbar-variant ALS.
Patients with dysphagia have a very poor prognosis; respiratory complications due to aspiration frequently result in death within 1 to 3 yr.
Progressive
muscular atrophy:
In many cases, especially those with childhood onset, inheritance is autosomal recessive. Other cases are sporadic. The disorder can develop at any age. Anterior horn cell involvement occurs alone or is more prominent than corticospinal involvement, and progression tends to be more benign than that of other MNDs.
Fasciculations may be the earliest manifestation. Muscle wasting and marked weakness begin in the hands and progress to the arms, shoulders, and legs, eventually becoming generalized. Patients may survive ≥ 25 yr.
Primary
lateral sclerosis and progressive pseudobulbar palsy:
Muscle stiffness and signs of distal motor weakness gradually increase, affecting the limbs in primary lateral sclerosis and the lower cranial nerves in progressive pseudobulbar palsy. Fasciculations and muscle atrophy may follow many years later. These disorders usually take several years to result in total disability.
Diagnosis
Diagnosis is suggested by progressive, generalized motor weakness without significant sensory abnormalities. Other disorders that cause pure muscle weakness should be ruled out:
When cranial nerves are affected, a treatable cause is less likely. Upper and lower motor neuron signs plus weakness in facial muscles strongly suggest ALS.
Electrodiagnostic tests should be done to check for evidence of disorders of neuromuscular transmission or demyelination. Such evidence is not present in MNDs; nerve conduction velocities are usually normal until late in the disease. Needle electromyography (EMG) is the most useful test, showing fibrillations, positive waves, fasciculations, and sometimes giant motor units, even in unaffected limbs.
Brain MRI is required. When there is no clinical or EMG evidence of cranial nerve motor weakness, MRI of the cervical spine is indicated to exclude structural lesions.
Laboratory tests are done to check for other, treatable causes. Tests include CBC, electrolytes, creatine phosphokinase, and thyroid function tests. Serum and urine protein electrophoresis with immunofixation for monoclonal antibodies is done to check for a paraprotein that is rarely associated with MNDs. Discovering an underlying paraproteinemia may indicate that the MND is paraneoplastic, and treatment of the paraproteinemia may ameliorate the MND. Antimyelin-associated glycoprotein (MAG) antibodies are associated with a demyelinating motor neuropathy, which may mimic ALS. A 24-h urine collection is done to check for heavy metals in patients who may have been exposed to them. Lumbar puncture should be done; elevated WBCs or protein levels in CSF strongly suggest an alternative diagnosis.
Serum Venereal Disease Research Laboratories (VDRL) tests, ESR, and measurement of certain antibodies (rheumatoid factor, Lyme titer, HIV, hepatitis C virus, antinuclear [ANA], anti-Hu [to check for anti-Hu paraneoplastic syndrome]) are indicated only if suggested by risk factors or history. Genetic testing (eg, for superoxide dismutase gene mutation or genetic abnormalities that cause spinal muscular atrophies) and enzyme measurements (eg, hexosaminidase A) should not be done unless patients are interested in genetic counseling; disorders detected by these tests have no known specific treatments.
Treatment
There is no specific treatment. However, an antiglutamate drug, riluzole 50 mg po bid, prolongs life in patients with progressive bulbar palsy. A multidisciplinary team approach helps patients cope with progressive neurologic disability.
The following drugs may help reduce symptoms:
In patients with progressive bulbar palsy, surgery to improve swallowing has had limited success.
Last full review/revision February 2008 by Michael Rubin, MD
Content last modified February 2008
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