Motoneuron diseases

Motor neuron diseases are characterized by progressive degeneration of the corticospinal tracts, anterior horn neurons, bulbar motor nuclei, or a combination of these lesions. Symptoms include muscle weakness and atrophy, fasciculations, emotional lability, and respiratory muscle weakness. Diagnosis involves conduction velocity testing, EMG, and exclusion of other abnormalities by neuroimaging and laboratory testing. Treatment of motor neuron disease is symptomatic.

Causes motor neuron diseases

There are several forms of motor neuron disease, and their etiology is often unknown. The nomenclature and symptoms depend on the localization of the predominant lesion. Among the myopathies simulating the clinical picture of motor neuron disease are lesions of the muscle membrane, contractile apparatus, and myocyte organelles.

[ 1 ]

Symptoms motor neuron diseases

It is customary to distinguish between damage to the upper (central) and lower (peripheral) motor neurons; sometimes (for example, in amyotrophic lateral sclerosis) both neurons are affected.

When an upper motor neuron is affected (e.g., primary lateral sclerosis), neurons are affected from the motor cortex to the brainstem (corticobulbar tracts) or spinal cord (corticospinal tracts). Symptoms include stiffness, difficulty, and awkward movements, first in the muscles of the mouth and throat, then in the extremities.

Lower motor neuron disorders affect the anterior horn neurons of the spinal cord or their efferent axons to skeletal muscles. Bulbar palsy affects only the bulbar nuclei of the cranial motor nerves in the brainstem. Facial weakness, dysphagia, and dysarthria are common complaints. Anterior horn neuron disorders, such as spinal amyotrophy, cause weakness and atrophy, fasciculations (visible muscle twitching), and cramps in the hands, feet, or tongue. Lower motor neuron diseases also include poliomyelitis and enterovirus infection, when the anterior horn neurons are affected, and postpolio syndrome.

Physical examination helps differentiate upper and lower motor neuron lesions, as well as weakness due to lower motor neuron lesions from weakness due to myopathies.

Forms

Amyotrophic lateral sclerosis (ALS)

ALS (Lou Gehrig's disease, Charcot syndrome) is the most common form of motor neuron disease. The disease begins with asymmetric cramps, weakness and amyotrophy of the hands (usually) or feet. Then there are fasciculations, spasticity, increased deep tendon reflexes, extensor plantar reflexes, stiffness of movements, weight loss, fatigue and difficulty controlling facial expression and tongue movements. Other symptoms include dysphonia, dysphagia, dysarthria and choking on liquid food. Then there are inappropriate, involuntary and uncontrollable (pseudobulbar syndrome) fits of laughter or crying. Sensitivity, consciousness, cognitive sphere, voluntary eye movements, sexual function and sphincter function are usually not affected. Death occurs due to paralysis of the respiratory muscles, half of patients die in the first 3 years from the onset of the disease, 20% live 5 years, and 10% - 10 years. Survival for 30 years is rare.

[ 2 ], [ 3 ], [ 4 ]

Progressive bulbar palsy

Disorders of the muscles innervated by the cranial nerves and the corticobulbar tracts cause progressive difficulties in chewing, swallowing, speaking, a nasal voice, decreased gag reflex, fasciculations and weakness of the facial muscles, as well as the tongue. When the corticobulbar tract is affected, pseudobulbar paralysis with emotional lability develops. With dysphagia, the prognosis is poor, respiratory complications due to aspiration lead to death within 1-3 years.

Progressive muscular atrophy

In many cases, especially if the disease begins in childhood, it is inherited in an autosomal recessive manner. In other cases, it appears sporadically. In general, the disease can develop at any age. It may affect only the neurons of the anterior horns or it may be more severe than the accompanying damage to the corticospinal tracts. The disease progresses more slowly than other motor neuron disorders. The earliest manifestation may be fasciculations. Muscle wasting and weakness begin in the hands, then spread to the arms, shoulders, and legs. Survival is usually greater than 25 years.

Primary lateral sclerosis and progressive pseudobulbar palsy

In progressive pseudobulbar palsy, tension and weakness gradually increase in the distal areas, affecting the extremities and muscles innervated by the caudal cranial nerves. Much later, fasciculations and muscle atrophy may appear. After several years, these disorders lead to complete disability.

Diagnostics motor neuron diseases

The disease should be suspected in cases of progressive generalized motor weakness without significant sensory impairment. Other neurological diseases that cause isolated muscle weakness include disorders of neuromuscular transmission and various myopathies. Acquired causes of motor weakness only include noninflammatory myopathies, polymyositis, dermatomyositis, thyroid and adrenal disorders, electrolyte disturbances (hypokalemia, hypercalcemia, hypophosphatemia), and various infections (eg, syphilis, Lyme disease, hepatitis C).

When cranial nerves are affected, a secondary cause is less likely. Lower and upper motor neuron signs and facial weakness are consistent with amyotrophic lateral sclerosis.

Electrodiagnostic studies are performed to exclude disorders of neuromuscular transmission and demyelination of nerves. In case of MN damage, the excitation conduction velocity is usually not affected until the late stage of the disease. The most informative is needle EMG, demonstrating fibrillations, positive waves, fasciculations, and sometimes giant action potentials of motor units, even in apparently unaffected limbs.

An MRI is required. In the absence of clinical and EMG data indicating damage to the cranial nerves, an MRI of the cervical spine is prescribed.

To identify potentially treatable diseases, a complete blood count is performed, the level of electrolytes, creatine phosphokinase, thyroid hormones, serum and urine protein are determined, electrophoresis with immunofixation for monoclonal antibodies is performed, antibodies to myelin-associated glycoprotein (MAG) are detected, and if there is a suspicion of heavy metal intoxication, their content is examined in daily urine. A lumbar puncture should be performed: an increased content of leukocytes or protein suggests another diagnosis.

At the slightest suspicion, a VDRL reaction for syphilis is performed, ESR, rheumatoid factor, antibodies to Borrelia, HIV, hepatitis C virus, antinuclear antibodies (ANA), antibodies to neuronal antigens appearing within the framework of paraneoplastic syndrome (anti-Hu) are determined. Genetic testing (for example, mutation of the superoxide dismutase gene) and determination of enzymes (for example, hexosaminidase A) are indicated only if the patient is interested in genetic counseling, and the results of these studies cannot in any way affect treatment.

[ 5 ], [ 6 ], [ 7 ], [ 8 ], [ 9 ]

Treatment motor neuron diseases

There is no specific treatment for motor neuron disease. The antiglutamate drug riluzole 50 mg orally twice a day prolongs life in bulbar amyotrophic lateral sclerosis. Progressive neurological dysfunction should be countered by specialists of various profiles. Physiotherapy helps to maintain muscle function. It is important to recommend orthopedic fixing bandages and walking devices. A speech therapist can select adequate communication devices. In case of pharyngeal weakness, food intake is a real threat and percutaneous endoscopic gastrostomy may be required.

If respiratory failure develops, a pulmonologist will recommend noninvasive respiratory support (eg, bilevel positive airway pressure), tracheostomy, or complete mechanical ventilation.

Baclofen reduces spasticity, quinine or phenytone may relieve cramps. Anticholinergics (eg, glycopyrrolate, amtriptyline, benztropine, trihexyphenidyl, hyoscine applications, atropine) reduce salivation. Amitriptyline and fluvoxamine are used for pseudobulbar lesions. In the late stages of these diseases, pain may require opioids and benzodiazepines. Surgery to improve swallowing in progressive bulbar palsy is of little use.

To determine the level of intervention that is appropriate, the treating physician should have frank discussions with the patient, family members, and caregivers early in the course of motor neuron disease. These decisions should be periodically reviewed and reaffirmed.