Management of patients with amyotrophic lateral sclerosis (ALS)
ALS (amyotrophic lateral sclerosis) or motor neuron disease is a neurodegenerative disorder in which motor cells of brain and spinal cord die. ALS belongs to the group of neurodegenerations such as Parkinson’s disease and Alzheimer’s disease. Spinal cord motor neurons die in ALS (that is why patients complain of weakness and atrophy of muscles, and muscle twitching) and brain motor cells (that is why patients have increased reflexes, increased muscle tone or spasticity, extensor plantar responses and other pyramidal signs).
Diagnosis of ALS is made by needle and stimulation myography (made 1 or 2 times, however, this technique is useful to monitor the disease progression and for prognostication of functional impairment), by spirometry (which should be done in the follow-up manner in order to initiate management of respiratory failure in time), magnetic resonance imaging of brain and spinal cord (in order to rule out focal lesions in the central nervous system that may cause signs and symptoms resembling ALS).
At present ALS is an incurable disease. Also it is progressive. Why is it so? Motor cells start to die far before the disease starts to manifest by its first signs and symptoms (weakness, atrophy and twitching in muscles). By the moment the disease starts to manifest quiet a small number of motor cells retains in the motor system for we might stop or cure this disease. However, slowing of the disease is possible. Besides, several symptoms are well treated. Progression may be rapid, moderate or slow. Some patients may fall into depression and may reject treatments after that. However, depression is curable. Psychiatrists, that collaborate with our clinic, may consult a patient and his relatives. That is why it is feasible to treat this disease.
In some cases of ALS cognitive functions are impaired (fronrotemporal dementia or frontotemporal cognitive impairment), that is why patients sometimes reject treatments, make mistakes in writing, loose interest to the surrounding world and their family. However, there are medications that decrease frontotemporal cognitive impairment.
The most resistant motor cells of the human organism are respiratory motor neurons. But they are also afflicted in ALS what may lead to death of a patient, if the patient is not given invasive ventilation. Before that moment non-invasive ventilation (NIPPV) should be used, and till present it is the only method of therapy that can slow the disease down onto a year or more. Devices for invasive and non-invasive ventilation, that will be offered to You in our clinic, are the most financially accessible at present in Russia.
Before to continue description of ALA management, recent advantages in understanding of ALS worldwide should be reviewed. Today it is known that functional impairment of many different genes may cause ALS (one gene in one person, other gene in the another, etc.). ALS may be familial, when at least two family members are affected in different generations or in the same one. Most frequently ALS develops in one family member, and its risk in other members is minimal. That is due to complex and not yet elucidated mechanism of ALS heredity. However, 15 genes are known to cause ALS to date.
If we see, that there are many ALS genes, it becomes obvious, that each gene envisages its own mechanism of the diseases development. That is why there is no and will never be discovered any medicine that may influence disease progression in all patients. In each case a specific damaged gene should be found, specific medicine should be done in each individual case. These medicines, however, are not yet elaborated. The only medicine that may slow disease progression, and it was proven in clinical trials. It is Rilutek. This drug is still not registered in Russia, but we may help You to buy it abroad. This drug decreases imbalance of excitatory amino acid in the nervous system and possess other unknown properties that slow ALS progression. However, this drug should be given to patients only until they participate in self service. This drug don’t do better. Slowing of progression is a statistical magnitude, calculated after comparison of large groups of ALS patients who received and who didn’t receive the drug. You can not feel slowing of progression. However, slowing of ALS by this drug is proven. Preserved speech and swallowing are also regarded “participation in self service”. However, if a patient cannot properly move his legs or his hands, and have impaired speech and swallowing, we will not recommend him this drug. At present another drug is being tried abroad. It blocks the damaged SOD-1 gene in ALS patients. This drug may become another specific ALS drug in the future.
People who promise You cure for ALS, in Russia or abroad, are swindlers. We frequently hear from our patients questions about stem cells, hyperbaric oxygenation, nutritional supplements, however, that does not help in ALS or may worsen the course of the disease. Many doctors prescribe for ALS many costly drugs “improving health in general”, which are absolutely useless in ALS, and some prescribe intramuscular injections to patients in whom muscles are atrophies what is potentially dangerous. Some medical offices may recommend a patient non-invasive ventilation at time is will never help. That never happens in our clinic. Our clinic does not promise cure. If You are ready to be monitored in the clinic in a follow up manner, we will suggest You effective treatment of ALS symptoms and a substantiated hope on slowing of the disease progression.
In the future drugs will be created based on disease mechanisms with underlying mutations of genes TDP-43, FUS, VAPB, Alsin, sentaxine, angiogenine, ubiquiline, profiline-1, C9ORF72. If we know, that drugs may be created in the future based on pathological action of those mutations, it is feasible to undertake genetic study, to determine whether an ALS patient or his relatives have such mutations. If You elucidate, that ALS is caused by a definite gene, a hope will appear. However the study does not warrant a positive results, as the majority of ALS genes is still undiscovered.
Besides, successful treatment of ALS is perhaps possible on the stage, when motor cells are already dying, but the disease itself is not yet manifested. The technique of tracing of this (preclinical) stage in people, who has mutations in ALS genes, but are still healthy, is being elaborated now abroad, and we have a concept on it. We may tell You about it.
Regrettably, there is still no state medical center for ALS patients in Russia, where doctors are offered satisfactory labor conditions, and patients are offered adequate recommendations and help.
The method of ALS management applied in our clinic is based on the International standard of ALS management and on personal experience of Gleb Levitsly who is the leading specialist in ALS in Russia. Gleb Levitsky, MD, PhD, is the president of Clinic “Real Health” and is director of Russian Charity ALS Foundation, is the author of comprehensive monograph in Russian «Amyotrophic lateral sclerosis: management and theoretical questions», and the author of a book «Information for ALS patients» (we will give it to You as a gift) and the author of web-site http://alsportal.ru with information for ALS patients in Russian. We recommend You to be acquainted with this web-site attentively. You may obtain a lot of useful information free of charge. Since 2006 Russian Charity ALS Foundation gave charity aids (adaptive equipment, non-invasive ventilation devices and even invasive ventilation device) to dozens of ALS patients. Clinic “Real Health” possessing a license on charity aids as well partakes in the work of Russian Charity ALS Foundation. Owing to successful activity of Gleb Levitsky as director of foundation You may count on charity aids such as adaptive equipment or may be NIPPV or invasive ventilation devices. However, primary and secondary appointment of ALS patients in our clinic is a matter of payment. However, understanding the tragic nature of the disease, we tried not to make the cost of such unique consultation very high. Charity aids may be given if present in the foundation at the moment of Your appeal and during the follow up. So, we recommend to be followed up in our clinic, not only to visit it once. Successful management of ALS is possible namely due to the follow up, examination and to making changes in the treatment plan. It should be noted that not all diagnostic and treatment tools are implicated in our clinic, and we may recommend You to visit other specialists.
What are those separate ALS symptoms that are well treated?
First of all, it is respiratory failure, which is determined by spirometry. If You take a look through Standards of Medical Care of Russia and pop into section about ALS, You will not find spirometry there. One should perform spirometry in ALS each 2-3 months/ When forced vital capacity (FVC) decreases below 80%, non-invasive positive pressure ventilation (NIPPV) should be started. НВЛ не заканчивается приобретением прибора. It is necessary then the doctor analyze a record how a patient breathes each 2-3 months and give recommendation to increase pressures. Many ALS patients and their relatives do not understand how coward the disease may be. A patient should not cease breathing with the device in summer. ALS does not go to its country house in summer. It goes to Your country house with You and progresses. Cessation of treatment may lead to the situation that You may not adapt to the device after such break.
Let us adduce some examples.
The patient О. with impaired movements in legs and shoulders got to know, that his spirometry is still well. He decided not to use NIPPV for s time (Figure 1). Five months later spirometry found such impairments of breathing, that the patient could no longer adapt to use NIPPV (Figure 2), albeit he was asked to come to check its in the next 2-3 months. It is important to understand, that a patient should be followed up in a recommended time intervals and should not disappear from the doctor’s field of view.
Figure 1
Figure 2
The patient А. with gait impairment, mild weakness in hands and mild speech impairment got to know that spirometry revealed breathing impairment in her (Figure 3). She purchased NIPPV device, used it for a month and then came to the follow-up spirometry. Spirometry showed improvement (lung capacities, and FVC in particular, increased onto 30-50%) (Figure 4). The patient was recommended to increase pressure in the device and to come in 2 months. But she didn’t increase pressures and came after 3 months. Spirometry estimates returned to baseline (Figure 5). After that patient disappeared from the doctor’s field of view at all.
Figure 3
Figure 4
Figure 5
The patient Sch. Purchased NIPPV device and started to use it since FVC was 70% (Figure 6). She appointed with the doctor each 2-3 months, made spirometry, and the doctor increased pressures in the device. A year later she had FVC that didn’t changed much (66%), and the disease itself as if slowed down (Figure 7).
Figure 6
Figure 7
The clinical trial of non-invasive ventilation conducted by Gleb Levitsky in Russia showed, that ALS patients who adapted to NIPPV and had cervical and lumbar onset of the disease survived significantly longer than those who didn’t adapt to NIPPV or didn’t use it (Figure 8). Analogous trials abroad several years before showed the same (Figure 9). Hopwever, the treatment with NIPPV was started since FVC lowered below 80%. In patients in whom LS started with speech impairment (bulbar ALS) disease was not significantly slowed down by NIPPV (it is known that only one third of patients with bulbar ALS and FVC 50-60% may adapt to NIPPV) (Figure 10). In those cases in order to manage respiratory failure we recommend to perform early tracheostomy and invasive ventilation, what will allow to evacuate thick secretions from trachea. Those secretions hamper ALS people to breath and to adapt to NIPPV. Appearance of a patient with invasive ventilation is shown on Figure 11. It is Natalya Rybakova who received invasive ventilation device from Russian Charity ALS Foundation. Appearance of a patient having NIPPV is shown on Figure 12.
Figure 8
Figure 9
Figure 10
Figure 11
Figure 12
It should be noted that in bulbar ALS patients weakness and atrophy of orbicular mouth muscle occurs what hampers them to keep spirometric tube in the mouth. Spirometry fails to detect ventilator function in them due to very low yield (Figure 13). In such cases bodypletismography is recommended. However, it also has limitations in bulbar ALS. It is not performed in our clinic, but we will recommend You where to do it.
Figure 13
One more symptom of ALS that can be effectively managed in swallowing impairment. Recommendation how to manage swallowing impairment on early stage are presented of . However, not waiting for late stage, an ALS patient should undergo gastrostomy, in order to receive the majority of foods through the tube in a stomach, not through the mouth, to prevent aspiration (when foods and liquids come to lungs). Aspiration may cause pneumonia that is fatal in 50% of cases. An ALS patient who objects gastrostomy or thinks that he can wait may die preterm. We give recommendations for safe swallowing after performance of three stage test on dysphagia (Figure 14). We also recommend You a surgeon who may perform You gastrostomy. You can inject ordinary foods in a tube or may use enteral feeding formula. Having in mind a patient’s height, weight and age we may calculate nutritional demand in an enteral feeding formula. It is called nutritional status study.
Figure 14
The important problem of many ALS patients especially with bulbar onset in sialorrhea. We recommend drugs which may effectively decrease sialorrhea. In some cases botulotoxin injection may help. In some cases irradiation of parotid glands may help (done in another clinic). In all patients with sialorrhea and/or swallowing impairment antibiotic prevention of aspiration pneumonia is indicated, what is not perceived by many doctors who encounter ALS patients.
Also an important problem is speech impairment. Speech recommendations and how to use alphabet table are presented on . In some cases speech therapist consultation is necessary. Soon a Russian speaking communicator will appear on Russian market. It is a communication tool for ALS patients in elaboration of which Russian Charity ALS Foundation takes part.
Motor deficits are the next complex problem in ALS. We recommend how to make orthopedic corrections, how to achieve muscle twitching and painful cramps to decrease, we may treat You with botulotoxine if You have spasticity. Physical exersizes useful in ALS are presented on http://www.alsportal.ru/healing/lechenie-dvigatelnih-narushenij/
Motor deficits may lead to peripheral venous thrombosis. Ultrasound Doppler of upper and lower extremities should be performed, recommendations are given how to prevent and treat such complications.
We assess cognitive functions in ALS, as well as emotional lability and depression using special clinical. Revealing this or that, we may advise You what drugs You can take to correct pathological changes. Those scores, as well as quality of life assessment and progression scoring by ALSFRSR allow to estimate efficacy of the treatment performed, to understand a patient more deeply and to support a patient in search of new sense in life.
On late stages of the disease (as well as on earlier stages when mobility is impaired) neurologist may visit You at home. Several recommendations allow to alleviate pain syndromes, and to manage sleeplessness.
Thorough analysis of symptoms and follow-up observation with timely implementation of professional advices allow to avoid unnecessary examinations, improve a patient’s quality of life, slow down the progression of the disease in most cases, and initiation of invasive ventilation and adequate care may prolong survival of a patient for many years.