Motor neuron disease (MND) is a group of diseases characterized by progressive degeneration of motor neurons in the primary motor cortex of the brain, brain stem, and spinal cord.

The disease may involve upper and lower motor neurons separately or together. Upper motor neurons start from the motor cortex of the brain and travel with long axons. Lower motor neurons originate from the brain stem and spinal cord and innervate skeletal muscles.

Motor neuron diseases can involve upper motor neurons, lower motor neurons, or both. They are classified according to the involvement priority. Symptoms vary according to the involvement of motor neurons.

Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is the most common adult-onset neurodegenerative disease involving motor neurons. It is a fatal disease with progressive muscle weakness and atrophy (amyotrophy), spasticity, and fasciculation as a result of degeneration of upper and lower motor neurons.

The involvement of motor neurons in the primary motor cortex, brainstem, and spinal cord determines the severity and prognosis of the disease. Death usually occurs when respiratory muscles are affected as a result of the degeneration of spinal motor neurons.

While the average lifespan after diagnosis is 3-4 years, 10% of people with ALS live 10 years or more. Stephen Hawking (1942-2018) fell ill with ALS at the age of 21, the genius physicist was thought to have a life span of a few years, but continued his life in a wheelchair for another 55 years and continued his scientific activities.

The prevalence of ALS is 5 per 100,000 and its incidence increases with age. It is low before age 40 and peaks at age 75. Peak starting age is between 55 and 75. It is slightly more common in men than women. 90-95% of ALS cases are sporadic, meaning there is no family history, and less than 10% are familial. C9orf72 and SOD1 gene mutations have been implicated in some of the familial ALS patients. There is no significant difference between the cases with familial and sporadic ALS in terms of clinical course and neuropathological findings. ALS cases show frontotemporal lobar degeneration.

Smoking is an important risk factor in sporadic ALS.

Symptoms of ALS

They are progressive muscle weakness and loss, muscle fasciculations, cramps, and spasticity. Symptoms of brain stem involvement are speech and swallowing disorders and drooling. The patient may also show fatigue, venous disorder, mental lability, depression, anxiety, and respiratory difficulties. Although ALS is an MND that is primarily a motor neuron degeneration, there is also dementia and cognitive impairment. Cognitive deterioration affects the patient's participation in treatment and the course of the disease.

Patients with MND with respiratory disorders should be followed up in terms of symptoms and progression with check-ups every 3 months. MIP (maximal inspiratory pressure), FVC (forced vital capacity), and arterial blood gas should be determined by a pulmonary function test.

The patient with ALS can control micturition and defecation. Patients whose heart muscles are intact can continue their sexual functions. Eye muscles are either unaffected or damaged too late.

Treatment: 

The treatment for ALS is medication, diet, speech and swallowing therapy, and rehabilitation. The only drug that slows down MND is Riluzole (Rilutek), which prolongs life by 2-3 months. Fatigue was reported in 26% of those taking Riluzole. Quinine sulfate can be used for muscle spasms and cramps, and baclofen and tizanidine can be used for spasticity.

Help from a dietitian and speech and swallowing therapist should be sought. If there is constipation, it is recommended to take apricot and prune juice in the morning, and laxatives and adequate fluids. A speech therapist can help with speech impairment and swallowing, as well as help with drooling to stop it.

Promising Treatments: 

New drugs to be developed, stem cell and gene therapies.

Rehabilitation: 

Maintaining range of motion, preventing contractures, strengthening, aerobic exercises, and assistive devices play an important role in the daily activities of the ALS patient and in maintaining a quality life.

Hereditary Spastic Paraparesis

It is also known as hereditary spastic paraparesis, familial spastic paraplegia, or Strumpell-Lorrain disease. It encompasses a group of clinically and genetically heterogeneous hereditary disorders characterized by slowly progressive spastic paraparesis. It is genetically classified as autosomal dominant, autosomal recessive, and X-linked. The most common form is pure autosomal dominant hereditary paraparesis.

The frequency of hereditary spastic paraparesis is around 2-7/100.000.

The disease occurs with gait disturbance. By progressing, the patient begins to walk with a cane and crutches. The patient may become wheelchair dependent. Bowel and bladder control may be impaired.

Medication for spasticity and botulinum toxin injection into spastic muscles can be used. Medication and diet are recommended for bowel and bladder control. Walking aid devices such as crutches and AFO are used in walking. Rehabilitation has the main role. Stretching and balance exercises are done. The upper extremity is strengthened. Walking robots are used. According to the patient's condition, arrangements are made in the home, workplace, and vehicle. Stem cell and gene therapy are in the experimental stage.

Progressive Bulbar Palsy 

Progressive Bulbar Palsy is a progressive degenerative disorder of the motor nuclei (especially the glossopharyngeal, vagus, and hypoglossal nerves) in the medulla. Atrophy and involuntary movements (fasciculations), speech disorder (dysarthria), and difficulty swallowing (dysphagia) occur in the tongue muscles. In adults, these symptoms may belong to bulbar-onset ALS, which some authors consider a subgroup of ALS. Speech and swallowing therapy play an important role in the treatment of the disease. If there is balance disorder and difficulty in using his hand, the patient is taken to physical therapy and rehabilitation, and work occupation sessions.

Spinal Muscular Atrophy (SMA)

SMA includes a large group of genetic neuromuscular disorders characterized by progressive degeneration of spinal lower motor neurons (i.e., alpha motor neurons in the anterior horn). Amyotrophy is present without signs of sensory or pyramidal tract involvement. It is a genetically heterogeneous condition; autosomal recessive (most common), autosomal dominant, and X-linked recessive. SMA is the second most common autosomal recessive disease. Its incidence is 1-2 per 10,000 live births.

Treatment is arranged according to the period of the disease and the needs of the patient. Rehabilitation starts from the beginning and continues in every phase of the disease. The patient's life is tried to be facilitated with assistive devices. SMA rehabilitation is done similarly to ALS rehabilitation. Nusinersen (Spinraza) is the first drug to be effective in the treatment of children (including newborns) and adults with SMA and was approved by the FDA in 2016, and its cost is quite high.

Postpolio Syndrome

It is characterized by unrelated late-onset muscle weakness and fatigue in the skeletal or bulbar muscles in individuals with a history of acute paralytic poliomyelitis attacks.

It is tried to increase the muscle strength and range of motion of the lower extremity involved in the treatment. Balance and walking exercises are done. Robotic rehabilitation can be benefited from walking training. Assistive devices and orthoses are prescribed according to the patient's needs.

SELECTED REFERENCES

- Fırıncıoğulları M, Yavuz B , Koç F. Ön Boynuz Tutulumuyla Giden Hastalıklar (Anterior Horn Cell Diseases). Arşiv Kaynak Tarama Dergisi .(Archives Medical Review Journal) 2016; 25(4):269-303

- Tiryaki E, Horak AH. ALS and other motor neuron diseases. Continuum (Minneap Minn) 2014;20:1185–1207

- Sena Aslan E, Erbaş O. Motor neuron diseases: Amyotrophic lateral sclerosis and spinal muscular atrophy. D J Tx Sci 2019;4(1-2):46-51.