The disease is characterized by the simultaneous involvement of anterior horn cells and pyramidal tracts, presenting with widespread muscle atrophy, fasciculations, and concurrent pyramidal tract signs.

bubble_chart Etiology

Since the cause of the disease is unclear, there are numerous theories regarding its etiology. Recent research supports immunological mechanisms in its pathogenesis, with various immunological theories proposed. Other potential causes include poisoning, metabolic disorders of trace elements and amino acids, and viral infections. Some cases exhibit hereditary characteristics. The incidence rate in Guam is 50 to 100 times higher than in other parts of the world, but no evidence of environmental toxins or abnormal dietary patterns has been identified.

bubble_chart Pathological Changes

The cervical spinal cord is a commonly affected site, with other areas of the spinal cord and motor nuclei of the brainstem also being eroded. Manifestations include shrinkage and sclerosis of anterior horn cells, a reduction in their number, and corresponding diminishment of the anterior roots compared to the posterior roots. Degeneration occurs in the motor nuclei of the brainstem, with partial loss of pyramidal cells in the motor cortex. Demyelination changes are observed in the corticospinal tracts. The pathological hallmark of the muscles is the presence of clusters of atrophic muscle fibers interspersed among normal muscle fibers.

bubble_chart Clinical Manifestations

The disease has a slow onset but progresses rapidly. Prodromal symptoms may include arm weakness, difficulty swallowing or speaking, calf weakness, or a combination of these, but the typical presentation is symmetrical weakness in the hands and arms, difficulty with fine motor skills, and gradual muscle atrophy. The interosseous muscles, lumbricals, and thenar muscles are affected early, with the condition spreading to adjacent and proximal muscle groups. Lower limb involvement occurs later or simultaneously with upper limb symptoms. Weakness and atrophy of the tongue, orbicularis oris, and masticatory muscles gradually develop, leading to dysphagia, dysarthria, drooling, or choking. Fasciculations are widespread in the limbs, trunk, mouth, tongue, face, and other areas, appearing intermittently. Pyramidal tract signs coexist with lower motor neuron symptoms such as muscle atrophy and fasciculations. Tendon reflexes in the limbs are hyperactive, and pathological reflexes appear. Sometimes, upper limb tendon reflexes are weakened or absent, while lower limb reflexes are hyperactive, leading to spasticity. Sphincter and sexual dysfunction are uncommon, and objective sensory impairment is rare. Most cases result in death within 2 to 5 years, with shorter survival times for those presenting with or predominantly exhibiting bulbar symptoms.

No drugs have been found to alter the progression of the disease. Many agents have been tried, including pancreatic extracts, antiviral drugs, phosphodiesterase inhibitors, snake venom, and immunosuppressants. Cricopharyngeal myotomy is used to reduce dysphagia. Tracheostomy is only performed for ventilator use. Gastrostomy or esophagostomy facilitates feeding.

bubble_chart Differentiation

Since this disease involves both upper and lower motor neuron signs, it needs to be differentiated from various conditions, such as spinal cord tumors, syringomyelia, muscular dystrophy, cervical spondylosis, and craniovertebral junction anomalies.

(1) Spinal cord tumors: Often present with radicular pain in the upper limbs but no widespread fasciculations. Sensory disturbances and subarachnoid space obstruction are present, and diagnosis can usually be confirmed by CT or MRI.

(2) Cervical spondylosis: May manifest with muscle atrophy, weakness, and fine motor impairment in the hands, as well as spasticity, hyperreflexia, and pathological reflexes in the lower limbs, closely resembling amyotrophic lateral sclerosis. Imaging signs of degenerative spinal disease are common in middle-aged and elderly individuals, making the two conditions easily confused. Cervical spondylosis typically involves sensory disturbances, at least subjective numbness or radicular pain. Widespread fasciculations are absent, and muscle atrophy does not occur in the lower limbs unless accompanied by lumbosacral radiculopathy. The Queckenstedt test often indicates obstruction.