People with ALS who have difficulty speaking may benefit from working with a speech therapist, who can teach adaptive strategies to speak louder and more clearly.
As ALS progresses, speech therapists can help people maintain the ability to communicate. Devices such as computer-based speech synthesizers use eye-tracking technology and can help people develop ways for responding to yes-or-no questions with their eyes or by other nonverbal means. Some people with ALS may choose to use voice banking while they are still able to speak as a process of storing their own voice for future use in computer-based speech synthesizers.
A brain-computer interface BCI is a system that allows individuals with ALS to communicate or control equipment such as a wheelchair using only brain activity. Nutritionists can teach individuals and caregivers how to plan and prepare small meals throughout the day that provide enough calories, fiber, and fluid and how to avoid foods that are difficult to swallow.
People may begin using suction devices to remove excess fluids or saliva and prevent choking. When individuals can no longer eat, doctors may advise inserting a feeding tube, which reduces the risk of choking and pneumonia that can result from inhaling liquids into the lungs. As the muscles responsible for breathing start to weaken, people may experience shortness of breath during physical activity and difficulty breathing at night or when lying down. Initially, NIV may only be necessary at night but may eventually be used full time.
Because the muscles that control breathing become weak, individuals with ALS may also have trouble generating a strong cough. There are several techniques to help people increase forceful coughing, including mechanical cough assistive devices.
As the disease progresses, individuals may need mechanical ventilation respirators in which a machine inflates and deflates the lungs. Doctors may place a breathing tube through the mouth or may surgically create a hole at the front of the neck and insert a tube leading to the windpipe tracheostomy. Although ventilation support can ease breathing problems and prolong survival, it does not affect the progression of ALS. Cellular defects. Ongoing studies seek to understand the mechanisms that selectively trigger motor neurons to degenerate in ALS, which may lead to effective approaches to halt this process.
Research using cellular culture systems and animal models suggests that motor neuron death is caused by a variety of cellular defects, including those involved in protein recycling and gene regulation, as well as structural impairments of motor neurons. Increasing evidence also suggests that glial support cells and inflammation cells of the nervous system may play an important role in ALS. Stem cells. Scientists are turning skin cells of people with ALS into stem cells that are capable of becoming any cell type, including motor neurons and other cells which may be involved in the disease.
NINDS-funded scientists are using stem cells to grow human spinal cord sections on tissue chips to help better understand the function of neurons involved in ALS. Genetics and epigenetics. Other studies are working to identify additional genes that may cause or put a person at risk for either familial or sporadic ALS. A large-scale collaborative research effort supported by NINDS , other NIH institutes, and several public and private organizations is analyzing genetic data from thousands of individuals with ALS to discover new genes involved in the disease.
By using novel gene editing tools, researchers are now able to rapidly identify new genes in the human genome involved in ALS and other neurodegenerative diseases. Additionally, researchers are looking at the potential role of epigenetics in ALS development. Epigenetic changes can switch genes on and off, which can greatly impact both health and disease. Although this research is exploratory, scientists hope that understanding epigenetics can offer new information about how ALS develops.
There is no cure and just 2 drugs are approved for the disease, each of which can slow progression somewhat in selected patients. In both familial and sporadic forms of ALS, the symptoms are the same. In the United States, men are almost twice as likely as women to develop the sporadic form. Sporadic ALS is diagnosed at an average age of 55 years, but the familial form of the disease may manifest much earlier.
The overall prevalence in the United States is approximately 5 per , individuals. The greatest risk factors for ALS are age and family history, with numerous genetic aberrations now identified. Since the first ALS genetic mutation was identified in , more than are now known to contribute to the disease.
The disease has a heterogenous presentation and is a diagnosis of exclusion, which can lead to diagnostic delays of up to 1 year Table 1. Diagnosis combines clinical examination, nerve conduction studies and electromyography, and laboratory tests, and is typically made using the revised El Escorial criteria Table 2. Younger patients and patients with limb-onset or delayed diagnosis typically have a longer survival. The pathologic hallmark of ALS is the death of upper and lower motor neurons, leading to degeneration of motor pathways.
Since , more than 80 randomized controlled trials RCTs on ALS have been published and just 2 drugs, riluzole and edaravone, have emerged as FDA-approved therapies for the disease. Reasons for the negative results of RCTs include an incomplete understanding of ALS pathogenic mechanisms, clinical heterogeneity of ALS progression, shortcomings of study design, and pharmacogenetic interactions. In terms of pathogenic mechanisms, it is generally accepted that several damaging processes trigger motor neuron degeneration.
These include protein misfolding and aggregation, oxidative stress, mitochondrial dysfunction, RNA processing impairment, neurofilament aggregation, loss of axonal transport, disruption of the neuromuscular junction, and axon demyelination.
Medical costs for patients newly diagnosed with ALS in the United States are substantial and increase rapidly with each disability milestone. Compared with other degenerative neuromuscular diseases eg, Duchenne muscular dystrophy, myotonic muscular dystrophy, spinal muscular atrophy , ALS is the costliest for medical, nonmedical, and indirect costs.
Of the direct medical costs, outpatient care was the largest cost driver, including hospital outpatient visits, physician visits, and physical and occupational therapy. Ventilator and wheelchair use were the main drivers for family out-of-pocket payments. They noted that multidisciplinary clinics improve patient outcomes and, where available, encourage referral.
Such teams should include a physician, physical therapist, occupational therapist, speech pathologist, dietitian, social worker, respiratory therapist, and nurse case manager.
Patients receive more aids and appliances and have a higher quality of life, with even a single visit to a multidisciplinary clinic providing benefits. Patients also have fewer hospital admissions and longer mean survival. Although beyond the scope of this article, a mainstay of treatment is to manage symptoms as the disease progresses and provide palliative care. Guidelines also recommend that clinicians talk with patients and their families about palliative care and end-of-life decisions.
The approval was based on 2 studies demonstrating a modest survival benefit of about 2 to 3 months. Riluzoleexerts an inhibitory action on glutamate release, inactivating sodium channels and interfering with downstream events resulting from transmitter binding at excitatory amino acid receptors. The riluzole group also demonstrated less muscle strength deterioration.
However, the therapeutic effect decreased between 12 and 21 months the end of the placebo-controlled period. Adverse effects AEs included asthenia, spasticity, and mild aminotransferase level increases. A significantly higher drug-related withdrawal rate among the study group was also observed. A larger follow-up trial of patients with fewer than 5 years of probable or clinically diagnosed ALS used tracheostomy-free status or death as end points.
Edaravone is an antioxidant and free radical scavenger that has been shown to reduce excess oxidative stress and cell death.
Subsequent dosing is done in cycles of daily dosing for 10 days of day periods, again followed by day drug-free periods. A second trial enrolled individuals who met the criteria of those demonstrating a benefit in the first study. A clinically significant smaller decline in function at 24 weeks occurred in the intervention group —5.
A post hoc analysis of an open-label follow-up of 65 edaravone-treated patients and 58 placebo-treated patients who then received edaravone for 24 weeks showed continued benefit out to 48 weeks in the 93 patients who completed the follow-up. The most frequent AEs were injection-site contusion, gait disturbance, and headache.
The results of edaravone in a real-world setting are mixed. A retrospective study of 22 patients treated with edaravone and 71 untreated patients with similar baseline demographic and clinical characteristics—albeit shorter disease duration in the treated patients—found similar ALSFRS-R, muscle strength, and respiratory function between the groups 6 months after the baseline visit.
An Italian retrospective study of patients who received a median treatment period of 6. However, no information about the baseline characteristics of these patients was provided. Those who develop difficulty speaking may benefit from speech therapy as well as speech synthesizers and computer-based communication systems. ALS patients gradually lose the ability to function and care for themselves. They may survive from two to 10 years after the onset of the disease, with about 20 percent of ALS patients living more than five years after diagnosis.
UCSF Health medical specialists have reviewed this information. Not all individuals with ALS develop the same symptoms or the same sequences or patterns of progression. However, all people with ALS will experience progressive muscle weakness and paralysis. In the early stages of ALS, the symptoms may be so minor that they are overlooked. Common symptoms include:.
In more advanced stages, ALS causes shortness of breath and difficulty in breathing and swallowing, which is what eventally lead to a person's death. Based on US population studies, a little more than 5, people in the US are diagnosed with ALS each year — approximately 15 new cases per day.
It is estimated that as many as 30, Americans have the disease at any given time. Most people develop ALS between the ages of 40 and 70, with an average age of 55 at the time of diagnosis. However, rare cases of the disease do occur in persons in their 20s and 30s.
Although the cause of ALS is not completely understood, recent research suggests that multiple complex factors contribute to the death of motor neurons.
Research published in suggests that smoking tobacco may heighten a person's risk for ALS. Diagnosing ALS is difficult because there is no single medical test for it. Also, since many neurologic diseases cause similar symptoms, these other conditions must be ruled out first, through clinical examinations and medical tests.
0コメント