What is ALS?

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurological disease that destroys nerve cells in the brain  and the spinal cord and causes disability. It is also known as Lou Gehrig’s disease. The term “A-myo-trophic” is derived from the Greek languagae with “A” meaning no, “Myo” meaning muscle, and “Trophic” referring to nourishment i.e. “No muscle nourishment.” No nourishment in muscles results in “atrophies” or wasting away. “Lateral” refers to the areas in a person’s spinal cord where portions of the nerve cells that signal and control the muscles are situated. Degeneration of the area results in scarring or hardening “sclerosis”) within the region. In ALS patients, wasting away of the muscles results in nerve cell (neurons) destruction which is responsible for controlling the voluntary movement of the muscle. The condition affects voluntary muscle movement such as chewing, walking, talking and breathing as well as functioning of the limbs.

What Causes ALS?

ALS causes death of motor neurons which control the functioning of voluntary movements and muscle control. Some examples of such voluntary movements include actions that are controlled by the muscles in the arms and legs. Upper motor neurons send messages from the brain to the spinal cord and lower motor neurons from the spinal cord to the muscles throughout the body.  ALS affects these upper and lower motor neurons located in the brain, spinal cord and brainstem. Degeneration of upper motor neuron causes tightness of the muscle causing spasticity whereas degeneration of the lower motor neuron causes muscle weakness, muscle atrophy (shrinkage of the muscles) and twitching.

Amyotrophic Lateral Sclerosis causes infographic

Causes and risk factors associated with Amyotrophic Lateral Sclerosis

Over time, the progressive degeneration of the motor neurons in the brain and spinal cord causes the neurons to shrink and eventually results in their demise. When the motor neurons are lost, the brain is no longer able to initiate, move and control muscle movement. Consequently, within a few years of diagnosis, ALS patients experience muscles becoming smaller and weaker affecting the ability to speak, eat, walking up steps, reaching for items and perform daily routine tasks.

Symptoms of ALS

ALS as a disease involves a gradual onset. The speed at which symptoms of ALS worsen become life threatening varies from person to person. The onset can be so subtle that the symptoms may go unnoticed. Early signs of ALS can be seen in the body parts depending on which muscles are getting affected. In earlier stages, ALS can cause varied symptoms in different people. Gradual onset, painless and progressive muscle weakening are the most common initial symptom in ALS. Such symptoms may include stiff muscles, muscle twitching, finger dexterity, cramps and weakness or wasting of intrinsic hand muscles and a gradual worsening in muscular strength resulting in difficulty in grasping a pen, lifting a cup, change in vocal pitch and others. In approximately 75 to 80 percent of the patients, ALS symptoms begin with arms, hands, and legs, such as tripping, stumbling, or awkwardness while running. Some of the ALS patients also experience foot drop and a “slapping” gait that interferes with daily work performance. People with ALS can experience difficulties in emotional and cognitive functioning, including bursts of involuntary and inappropriate laughing or crying, depression, impaired critical thinking, or abnormal social behaviour.

Amyotrophic Lateral Sclerosis symptoms infographic

Symptoms associated with Amyotrophic Lateral Sclerosis

Since the neurodegenerative disease attacks only motor neurons, the sense of sight, touch, hearing, taste and smell does not get affected and for many of the people, even muscles of the eyes and bladder usually stays unaffected. Since generally ALS does not affect bowel or bladder control, and thinking ability, so the patients remain actively involved with their circle of friends and family. On the other hand, some of the individuals may experience muscle cramps that may cause discomfort and result in difficulty with language or decision-making, and growing evidence suggests that with progression in the disease, some of the patients may even develop dementia. Some of the ALS patients may develop nerve disease or damage and become prone to risk of developing pneumonia especially during advanced stage of the disease.

With progression of the disease, the patient becomes paralysed and can experience difficulty in speaking, swallowing, and eventually, breathing. When the breathing muscles get affected, eventually, the respiratory system of the people with ALS weakens and patients might lose their ability to breath on their own leading to a need for permanent ventilatory support in order to assist them with breathing.  As the disease progresses further and the nerve cells get destroyed, muscle atrophy becomes more apparent and muscle cramps more common. In more advanced stages, people with ALS often experience voice changes, including hyper nasality and development of a strained or strangled vocal quality. Speech may be lost completely and patients may experience drooling and have difficulties in swallowing. Some other common symptoms include slurred speech, hoarseness, poorer speech volume, aspiration of food and choking during a meal.

The rate at which progression of ALS happens varies from person to person. Moreover, not all the people with ALS experience the same symptoms or the same sequences or patterns of progression. Progressive weakening of the muscle is experienced universally. With an average survival time of three to five years for people with ALS, half of all people affected with ALS live at least three or more years after diagnosis, twenty percent live five years or more and around ten percent live more than ten years. There is some evidence that clinical management interventions, and possibly other treatments and drugs under investigation are helping people with ALS to live longer.

Types of ALS

ALS manifests in many different forms but two of the most common ones include familial and sporadic ALS. Some of the other forms of ALS include Guamanian ALS and ALS-parkinsonism-dementia complex. Types of patients with ALS include familial or inherited ALS and sporadic ALS. Familial ALS is a family lineage disease which is inherited implying that it gets passed on from the parents to the children. This is of very rare type since only five to ten percent of ALS cases are inherited and generally needs only one parent to carry the genetic mutation leading to disease. Familial ALS is a result of mutations existing in more than a dozen genes.

C9ORF72. Some of the symptoms which individuals may experience include motor neuron and dementia symptoms. Another twelve to twenty percent of familial cases result from mutation in the genes that provides instructions for the production of (SOD1) enzyme that binds to copper and zinc molecules to break down superoxide radicals. In order to avoid damage to the cells, these molecules must be broken down regularly. These molecules get accumulated in nerve cells and result in their destruction due to malfunctioning of SOD1 enzyme. People with this ALS start showing initial symptoms at much a more earlier age than shown in sporadic ALS.

Sporadic ALS is non inherited i.e. it doesn’t run in the family and may affect anyone, anywhere. It occurs in people with no history of the disorder in their families. In this type, patients usually initially develop symptoms of this condition in their late 50s or early 60s. The cause of this type of ALS is not very well understood but may be attributed to a combination of genetic risk and environmental factors. Around ninety percent or more of the people have sporadic type of ALS. Genetic variations can influence one’s susceptibility to ALS even if they don’t really cause ALS. Scientists and researchers mention chemical imbalance, disorganized immune response and protein mishandling as some of the possible causes of non-inherited forms of ALS.

People with this ALS type usually have chemical imbalance i.e. higher than normal levels glutamate, a chemical messenger in the brain and in the spinal fluid around nerve cells. Such high levels of glutamate are toxic to some nerve cells and may lead to ALS. Moreover, protein mishandling or incorrect processing in the nerve cells can lead to a gradual accumulation of abnormal forms of these proteins in the cells, seriously affecting or killing them. According to the scientists and researchers, ALS results from the inability of protein system (ubiquilin2) to repair nerve cells that tell the muscles what to do. In those suffering with the disease, ubiquilin2 does not function properly leading to an buildup of the damaged proteins and ubiquilin2 in critical nerve cells in the spinal cord and the brain. This is also a result of disorganised immune response. Sometimes the immune system of a person with ALS begins to attack the healthy cells leading to destruction and death of the nerve cells.

An extremely high incidence of Guamanian ALS was observed in Guam and the Trust Territories of the Pin the 1950s. The reasons behind its occurrence it still not completely known. ALS-parkinsonism-dementia complex is a very rare form of ALS since it often runs in the family. It is characterised by symptoms of ALS as well as a pattern of movement abnormalities called parkinsonism. This condition includes symptoms such as unusually slow movements (bradykinesia), stiffness, and tremors.

ALS infographic

Facts and figures related to ALS

Prognosis of ALS

There are several factors which have been identified responsible for such variability in symptoms of ALS. For instance, those ALS patients with initial bulbar symptoms carry worst survival outlook when compared with those with spinal onset for, of ALS which affects the limbs and the trunk of patients. On the other hand, the outlook for respiratory onset ALS, the form that initially affects the respiratory system, is particularly poor. Prognosis gets worsened due to the form of ALS that exists in the patient. Another factor which worsens the prognosis id development of the disease in later part of life. Those who develop it before their 40s, live much more longer. Prognosis in the patient also gets affected by type of ALS i.e. whether ALS is inherited or not. Those patients with an inherited type of ALS disease caused by gene mutation A4V affecting SOD1 enzyme, survive only twelve months. Other mutations of the same gene result in a less aggressive disease.

Rapid deterioration in a person’s capacity to undertake routine tasks and a shorter life can be predicted through weakness in the neck muscle. Experts in the field of ALS have varying opinion about whether three other factors affect the progression of the disease and patient’s survival. It includes gender, time taken for to diagnose a person experiencing symptoms, and whether ALS exhibits itself in the upper or lower limbs. The question of whether a delay in diagnosis impacts progression of ALS and patients’ survival rate becomes complex by the likelihood that those who go to a doctor, later may have a disease with slower progression. In addition to the movement problems associated with ALS, There has been growing recognition that it ALS results in movement related problems such as thinking. Around fourteen percent of the ALS patients develop frontotemporal dementia, implying shorter survival because of the condition and up to half experienced subtle cognitive damage.

Diagnosis of ALS

According to the ElThe diagnosis of ALS disease is based Amyotrophic lateral sclerosis (ALS) is difficult to diagnose. Diagnosis of ALS refers to clinically definite, probable, possible, or suspected, depending on the progression of degradation of LMN and UMN and the outcome of electromyography testing. There is neither any cure nor any single test that can help in definitive diagnosis of amyotrophic lateral sclerosis (ALS) since it shares many common symptoms with other neurological diseases. However, the presence of both upper and lower motor neuron symptoms suggests that someone might be having the neurodegenerative disease. Moreover, individuals might benefit through seeking second neurological opinion since a definitive ALS diagnosis is not always possible. For a complete ALS diagnosis, clinical tests need to be undertaken to rule out other neurological diseases based on the symptoms shown by the patient.

The diagnosis of ALS disease is based on the period of observation to track the progression of the symptoms in the patient and the clinical tests conducted to help in ruling out other diseases by the doctor. Such observation of symptoms in the patient can take up to a year resulting in a diagnosis spread over twelve to fourteen months in the United States. The tests are conducted at the discretion of the physician, generally based on the results of tests and physical examination. There are many other diseases with similar symptoms as ALS and most of them are treatable. For this reason, the ALS Association recommends that a person diagnosed with ALS should seek a second opinion from expert who has experience in diagnosing and treating people with ALS.

According to the El Escorial criteria, by the World Federation of Neurology (WFN), conditions for diagnosis of ALS include signs of degeneration of the upper motor neurons (UMN) and lower motor neurons (LMN) in the spinal cord, brainstem and in the brain respectively, the progressive spread of symptoms within a region, or to other regions of the patient’s body, no proof of other disease processes that could justify the symptoms. Motor neurons are nerve cells whose cell body is situated in the spinal cord and whose fiber (axon) projects outside the spinal cord in order to control the muscle movement. A full and complete diagnostic test for ALS includes procedures as given below:

  •       Electromyography (EMG), helps in assessing the electrical activity in the muscle. For the diagnosis of ALS, abnormal EMG results can help to confirm LMN degeneration.
  •       Nerve Conduction Velocity (NCV) study excludes disorders that effect the peripheral nerves and just measures the capacity of a nerve to transmit an electrical signal to other body parts.
  •       X-rays including Magnetic Resonance Imaging (MRI), is used to produce images of the brain and spinal cord to assist in the diagnosis of the disease. Although ALS patients usually reflect normal MRI scans, however this can help in revealing other treatable causes behind the symptoms, like syringomyelia (a cyst in the spinal cord).
  •       In very few and rare cases, a muscle or nerve biopsy is performed involving process of removing a small section of muscle from the patient using local anesthesia and examined for abnormalities.
  •       Myelogram of cervical spine
  •       A thorough neurological examination
  •       Blood and urine testing for instance for high resolution serum protein electrophoresis, thyroid and parathyroid functioning and 24-hour urine collection for heavy metals.
  •      Spinal tap (or lumbar puncture) to exclude inflammatory nerve conditions.
  •       Tests for infectious diseases such as human immunodeficiency virus (HIV) and human T-cell leukemia virus (HTLV), which can cause symptoms similar to the ones as experienced in ALS.

Treatments do exist which can help in extending the length and quality of life of patients. For example, although there is no cure for ALS, Riluzole can help to extend a patient’s survival by three to six months and Radicava can slow the deterioration in functioning in the ALS patient.

Stages of ALS

Since rate of progression of the disease differs with patients, Patients may not experience the same symptoms. Although some ALS patients might experience weeks to months of no further loss of function, or even recover some of the functions, however significant improvement lasting a year or more occurs only in less than one percent of the patients. Such progression has been divided into three very distinct stages namely early, middle, and late. During the early stage of ALS which is also associated with muscle loss or atrophy, patients experience initial symptoms such as muscle weakness, tightness, cramping, or twitching.

Symptoms at this stage make daily tasks difficult to execute such as buttoning clothes or opening a can of food. Although they are usually limited to a particular body part, beginning and from the the arms or hands in the initial phase, however, they may also first appear in the leg. Disease that onsets from the arms or legs is called “limb onset” ALS. The muscular issues may result in fatigue, poor balance, slurred words, loss of grip strength, or to trip or fall when walking. ALS patients with symptoms in the hands or arms may face difficulty in taking up simple tasks requiring manual dexterity such as writing, buttoning a shirt, or turning a key in a lock.  In those with symptoms appearing in the leg, people may experience clumsiness when they walk or run, or they may experience tripping or stumbling more often.

During the middle stage of ALS, muscle weakness and atrophy spreads to other body parts. Some of the  muscles become paralysed, while others lose their strength. Some of the muscles not used very frequently may result in becoming permanently shortened, leading to contractures in which joints (e.g., elbows) are unable to fully straighten. People may also develop difficulties in walking, and in swallowing, chewing food, which increases their risk of choking. Increasing muscle weakness also results in problems such as difficulty in speaking and breathing, and uncontrollable and inappropriate laughing or crying, also known as pseudobulbar affect. Most of the people with ALS retain higher mental and reasoning abilities, and are very much aware of their progressive loss of muscular functioning.

Late or advanced stage of ALS results in paralysis of most of the voluntary muscles. Eating, speaking, and breathing gets affected when the muscles of the mouth and the throat and those involved in process of breathing become paralysed. Consequently, feeding tube is used for eating and drinking and ventilator is used for assisting in breathing. Most people with ALS die due to respiratory failure, and the prognosis is usually three to five years after the first symptoms start appearing. Some of the less common causes of death may result from malnutrition, pulmonary embolism, heart arrhythmias, and pneumonia due to aspiration.

Physiology of ALS

ALS disease generally strikes people between the ages of forty and seventy, and as per the estimates there are more than 20,000 Americans living with the ALS disease at any given point in time with some fluctuations in this number. Military veterans are double as likely to be diagnosed with the disease as the general public due to reasons not known yet. Some of the notable individuals who have been diagnosed with ALS include baseball great Lou Gehrig, theoretical physicist, cosmologist and author Stephen Hawking. In the recent years, research has generated new wealth of scientific knowledge and understanding about the physiology of the ALS disease. At present, there is one FDA-approved drug available called riluzole, which helps in slowing down the progression of ALS in some of the patients. There is no cure or treatment available which can halt or reverse ALS but researchers and scientists have made significant progress in contributing towards learning more about ALS disease. Furthermore, ALS patients may experience a better quality of life even when having the disease by participating in support groups and by attending certified or recognized treatment centers. These centers help by providing a national standard of best-practice multidisciplinary care to manage the signs and symptoms of ALS disease and help ALS patients in maintaining their own independence as much as possible. Practice Paramater Update by American Academy of Neurology, discusses study findings that have shown that participation in such a multidisciplinary clinic may assist in prolonging the survival and improving the quality of life.

Incidence and Prevalence of ALS

ALS disorder affects the functioning of nerves and muscles of those between the ages of forty and seventy with an average age of 55 when ALS is diagnosed. However, some of the people in their twenties and thirties may also get the disease. Usually ALS occurs in higher percentages as men and women grow older. ALS occurrence is also twenty percent more common in men than in women. However, with increasing age, the incidence of ALS becomes more equal between both men and women. ALS Association projects the incidence rate of ALS to be 1.8 to 2 per 100,000 people, which implies 5,760 to 6,400 new diagnoses per year. The incidence of ALS increases with age usually starting in the 40s and continuing till the age of around 80 years. However, this does not cross 92 percent out the chances of people in their early 20s and 30 s to get affected with ALS. According to the estimates, there are around four to six people per 100,000 living with ALS at any given point in time.

ALS incidence infographic

Facts and figures related to ALS incidence

Facts about ALS

Given below are some of the facts that one should know about ALS:

  •       ALS is not contagious implying that in can’t spread from one person to another by touching, sneezing etc.
  •       Although from the time of diagnosis, the life expectancy of a person with ALS averages about two to five years, this disease is still variable, and many people can live with the disease for five years and more. More than half of all the ALS patients live more than three years after diagnosis.
  •       Once the onset of ALS takes place, it almost always progresses, ultimately affecting the capacity of the patient with ALS to walk, dress, write, speak, swallow, and breathe and thus, shortening their overall life span. The pace and the order in which ALS occurs and progresses varies from person to person. With an average survival time of 3 years, about twenty percent of the people with ALS live for five years, 10 percent survive for ten years and around five percent live for 20 years or more.
  •       Progression does not always follow a straight line in an individual. It is not uncommon to have periods lasting between weeks to months with very very little or no loss of function at all. There are very rare and few examples in which there was significant improvement and recovery of lost function. These ALS “arrests” and “reversals” are unfortunately generally transient. Less than around 1 percent of the patients with ALS will have significant improvement in function lasting for 12 months or more.
  •       Approximately 6,000 people are diagnosed with ALS each year in the U.S. The incidence of ALS is two per 100,000 people, and it is estimated that there are more than 20,000 Americans who may be having ALS at any given time.
  •       ALS happens all throughout the world with no racial, ethnic or socio-economic boundaries and can affect anyone.
  •       Military veterans are approximately twice as likely to develop ALS.
  •      The onset of ALS often involves weakness or stiffness of the nerve muscles as initial symptoms. Progression of weakness, wasting and paralysis of the limb muscles and trunk muscles as well as those that control vital functions such as speech, swallowing and later breathing generally follows.
  •       Technology is changing rapidly and there can be substantial costs associated with the medical care, equipment and health caregiving at home in the advanced stage of ALS disease. Thus, it becomes vital to be knowledgeable about one’s health plan coverage and other programs for which they might be eligible, including Social Security Disability, Medicare, Mediciad and Veteran Affairs benefits and others.

Genetic Counselling and Genetic Testing for ALS

It is suggested that if there is more than one person living with ALS in your family and /or front temporal dementia in the family or if someone was diagnosed at a younger age of 45 years of age, then one should fix his/her appointment with the genetic counsellor periodically for updates. Meeting genetic counsellor involves taking a note of detailed medial history of the family, evaluating risks and discussing the effects of genetic testing. A genetic counsellor can assist in working out way through the pros and cons of genetic testing based on the concerns and values. Genetic counselling may not always result in genetic testing. DNA Banking which helps in storing a person’s blood so that it can be available for testing and investigation in the future is one useful option for people with ALS not having an identifiable genetic mutation.

Genetic testing assists in determining the causes behind FALS running in a family. Testing seems to be most useful in a person already diagnosed with ALS. Around sixty to seventy percent of the individuals with FALS do not have a positive genetic test result. Those families with FALS where mutation isn’t identified may have FALS caused by some undiscovered gene. FALS diagnosis can’t be eliminated and other family members maybe still prone to developing ALS. Biological family members who don’t have symptoms can be tested to check whether they inherited the genetic mutation or not only if the mutation has been identified. This is known as predictive testing and some of the medical centers may require a neurological exam, psychological assessment and counseling prior to conducting such predictive testing.

If a person in the family with ALS has no identified genetic mutation resulting in negative genetic test result, then testing family members without a diagnosis of ALS will not provide more information. If no one in the family with ALS is available for genetic testing, a negative test result in an unaffected person is difficult to interpret. Genetic testing might help in providing explanation about whether there is a genetic cause of ALS within the family. It also helps the family members to identify and diagnose through testing whether they carry the genetic mutation causing the disease or not. It might also offer couples planning for having children to conduct prenatal testing in advance to know whether genetic mutation exists or not. However, genetic testing can’t change the existing medical treatment, can’t diagnose ALS in people without the symptoms and it can’t tell whether a person without the symptoms about when they would start showing the symptoms or the progression of ALS.

Genetic testing for all the known FALS genes can cost about $1600 to $5000. It usually costs $500 – $1500 for genetic testing for one gene. The cost for the test for familial mutation reduces to around $400 when the genetic mutation in the family is already known. Genetic testing might or might not be covered under insurance depending on different parts of the world. Genetic testing usually involves taking sample of blood or spitting in a special type of tube in the doctor’s office or in a lab associated with the doctor’s office by a healthcare professional. Results can take anywhere between few weeks to a few months depending on the type of testing ordered by the health professional. Results should be communicated in person at a follow-up appointment or by telephone by the genetic counselor or doctor who ordered the test. Genetic testing of children under age 18 is not recommended since FALS is usually an adult-onset condition.

Genetic testing protocols may differ among clinics as some may offer testing for different genes, while others might do it for research basis only. Results can be difficult to interpret at times since test results are not always straightforward and there are still many genetic changes that the researchers as well as the scientists do not understand yet. Genetic testing is a personal choice and people get the testing done to better understand the reasons why they got the disease and help other family members. Some unaffected people want to know if they are prone or at risk of getting ALS, while others would prefer not to know. Consultation with a genetic counsellor can help in deciding whether the testing is needed or not.

Treating ALS

In the midst of the development of a cure for ALS, Regenerative Treatment is considered to be the most promising alternative method when it comes to treating ALS and other neurodegenerative illnesses. It has an ability not only to improve the condition of the patient and prevent secondary complications, but also to reverse neurological damage. The Treatment Protocol centres around cell transplantation. The cells in question have the ability to regenerate and replicate when activated in the right circumstances and can become almost any specialised type of cell, making it a highly effective treatment method for neurodegenerative diseases. Cellular Therapy is aimed to increase neuron survival as well as prevent gliosis in the areas damaged by the death of motor neurons. Moreover, Regenerative  Treatment also has an ability to regulate the immune system’s response against the nerve cells and release growth factors, which promote cell growth, differentiation, and stimulate the brain’s own cells to promote tissue repair for a speedy recovery process.

In an effort to boost the efficacy and achieve optimal effects of Cellular Therapy , ALS patients always undergo an extensive Rehabilitation Program, which plays an extremely crucial role in the patient’s recovery process. Rehabilitation Programme helps the body to maintain its functions and permits the patients of more independent and safer lives. Also, as a result of the rehabilitation, the otherwise deteriorating muscles are kept active and the progression of the disease is tremendously slowed down.

The Rehabilitation Techniques vary from Physiotherapy, Occupational Therapy, Acupuncture, Aquatic Therapy, Transcranial Magnetic Stimulation (rTMS), and Special Diet Plans, each with its own desired effect.

Many ALS patients who have received Regenerative Treatment have shown significant improvements in motor function, muscle tone, muscle strength, speech, ability to swallow, balance, coordination as well as improvements in their fine and gross motor skills. Moreover, following the process of Cellular Therapy, the progression of the disease has often been reported to have been significantly slowed down.