Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (abbreviated ALS) is a degenerative disease of the motor nervous system. It is also called amyotrophic lateral sclerosis or myatrophe lateral, English and Motor Neuron Disease, also known as Lou Gehrig's disease or after the first describer Jean- Martin Charcot Charcot 's disease.

• 6.1 Neuroprotective therapy
• 6.2 Symptomatic therapy 6.2.1 Muscle cramps ( Cramps )
• 6.2.2 swallowing disorder
• 6.2.3 salivation
• 6.2.4 speech disorder and communication
• 6.2.5 Pathological laughing and crying
• 6.2.6 Respiratory disorder
• 6.2.7 depression, insomnia and anxiety

Symptoms

ALS occurs in a progressive and irreversible damage to or degeneration of the nerve cells (neurons) responsible for the muscle movements. These are also referred to as a motor or motor neurons. Both the so-called upper motor neurons be affected motor nerve cells in the motor cortex ( motor cortex ) are, as well as those marked as second motor neurons of the anterior horn cells of the spinal cord or the motor cells of the brain stem in the cranial nerve nuclei. The extensions ( axons ) of the first motor neurons pull the lower motor neurons, which in turn move with their projections to skeletal muscle and innervate them. By the degeneration it comes to increasing muscle weakness (paralysis, paresis ), with muscle wasting ( amyotrophy ) - by damage to the lower motor neuron - and with an increased muscle tone (spasticity ) - by damage to the upper motor neuron - goes hand in hand. Due to the paralysis of the muscles results, among other things speed, speech and swallowing difficulties, impaired coordination and weakness of the arm and hand muscles, thereby increasing restriction in activities of daily living.

Amyotrophic lateral sclerosis is incurable. The focus of therapy is on a relief of symptoms and psychological care. The survival time of an average of about three to five years. Death often occurs as a result of pneumonia, whose formation is favored by the increasing dysphagia and paralysis of the respiratory muscles.

Frequency and occurrence

Amyotrophic lateral sclerosis is a worldwide occurring and total rare disease. 100,000 people are diagnosed per year, about one to three new ALS (incidence). The prevalence - that is, the number of diseased people at a given time - is provided with 3 to 8 per 100,000.

In men, the AS is more common than in women ( the gender ratio is about 1.5:1 ). Most cases occur between the ages of 50 and 70 years, with the mean age of onset is 56 to 58 years. Rare ALS affects younger patients between 25 and 35 years.

Although the ALS occurs roughly comparable common worldwide, there are some important thereof for research exceptions. So is a variant of the disease, which offers besides the symptoms of ALS and symptoms of Parkinson's disease and dementia, particularly commonly found on various islands in the Pacific. The Chamorro in Guam, the Auyu and Jakai in West New Guinea and on the Kii Peninsula in Japan, the incidence of this so called ALS-Parkinson's -dementia complex is up to 100 (up to 1000 partly in Guinea) per 100,000 people. Detecting continues to be a decline in the incidence in these areas during the last decades. As the affected populations are genetically independent of each other, in addition to genetic factors and environmental factors are discussed as a cause of infections in the respective populations.

It is also noteworthy the increased relative abundance in football players. A study by the University of Pavia found an increased risk for progression to AS before the 49th year in a study of Italian professional football players.

The name Lou Gehrig's disease derives from the fact that the popular New York Yankees baseball player Lou Gehrig, who is still one of the most successful representatives of his sport, fell ill during his playing career at AS. The disease forced him to a series of 2,130 consecutive games cancel in 14 years and was diagnosed shortly after his 36th birthday to ALS, he finished his career in 1939. Gehrig died two years later at the age of 37 years. The sympathy for the fate Gehrig made ​​the rare disease known to a large public for the first time and for the complicated name, the simplicity quickly naturalized half a the name of Lou Gehrig's Disease ( Lou Gehrig's disease ).

Cause

The cause (etiology ) of the disease is unclear. Genetic factors are found in most ALS patients, whether they are the sole trigger is unknown. Most cases occur sporadically, ie without familial predisposition to ( sporadic ALS, sALS ). However, in a small proportion of cases (5-10%), there is a family history (familial ALS, fALS ). Three groups of mutations in different genes ( TARDBP, C9ORF72, VAPB, FUS, SOD1 ) are found in a majority of cases. They lead to pathological accumulation or premature degradation of a misfolded protein, respectively (TDP -43, FUS or SOD1 ), which ultimately ( the tau protein as in the tauopathies ) triggers neurodegeneration.

In about 20 % of families are an expansion of a repetitive gene segment of C9ORF72 is detectable in a further 10 % of the affected families mutations of the gene coding for a superoxide dismutase SOD1 gene are detectable. Frequently here is an autosomal - dominant inheritance. A number of other genes has been associated with a family appearance. Thus, mutations of the TAR DNA binding protein gene ( TDP -43 ) have been described that have been degraded rapidly in vitro and elicited an increased apoptosis in neural cells. In a familial form with X- chromosomal inheritance of mutations UBQLN2 gene could be detected. This gene encodes Ubiquilin 2 - a protein that is involved in degradation of ubiquitinated proteins in the regulation of the - and may play a role in the sporadic ALS.

Another factor of the disease could be sought in excitotoxic events ( overdrive ) at the NMDA receptor. D-serine, the transmitter is a co- agonist at this receptor and increases the receptor affinity of the agonist glutamate. An overstimulation of the NMDA receptor may have neurotoxic consequences. A conditional by a pathological mutation of the enzyme D -amino acid oxidase slowed serine degradation could be the physiological concentration of these D- amino acid to rise sharply.

Disease

Amyotrophic lateral sclerosis is a - especially in the early stages - very variable disease, which is characterized by degeneration and consequent malfunction of the first and second motor neuron. This has deficits of muscles result. The clinical presentation is accordingly characterized by a combination of spastic paralysis and atrophy of the muscles. Depending on the location of the injury to the motor pathways it comes to functional impairment of the muscles of the upper and lower extremities, the bulbar muscles and the core muscles.

Spastic paralysis caused by the degeneration of the first motor neuron and lead to functional limitation by increasing the muscle tone. Depending on the location of the injury, this is shown among other things by a spastic and slower gait, impaired manual dexterity as well as bulbar symptoms, such as speech and swallowing disorders, difficulty opening the mouth, through to lockjaw ( trismus ). The spastic speech disorder is characterized by a strained and slowed speech.

The damage to the lower motor neuron leads to atrophic paralysis. Due to the increasingly restricted innervation of the muscles is reduced (atrophy ) and there is muscle weakness. In addition, fasciculations and painful muscle spasms ( Cramps ) are typical. If the bulbar muscles affected, is it due to the muscle weakness, also to speech and swallowing disorders. Also typical are fibrillations of the tongue.

Chronic juvenile ALS

The chronic juvenile ALS is a variation of the disease that takes an extremely slow pace. The most famous patient is the British physicist Stephen Hawking, in which ALS was diagnosed in 1963.

Diagnosis

Patients usually leads an increasing muscle weakness, muscle wasting ( atrophy ) or non-motion effective muscle twitches ( fasciculations ) to the doctor. Muscle twitching alone nearly always called benign fasciculations dar. Excluded from the failure of the eye muscles, otherwise the disease can show anywhere on the body first. Amplified When studying the simultaneous occurrence of signs of flaccid and spastic paralysis of the suspicion of the diagnosis of amyotrophic lateral sclerosis. It is named after a muscle wasting, particularly to look at the hand muscles. Typical malignant muscle twitches ( fasciculations ), such as when sticking out the tongue (there are fibrillations ). Malignant muscle twitches are different from the much more frequently occurring benign muscle twitching by their irregularity and lower frequency. The reflexes remain triggered even in the paralyzed parts of the body for a long time, they are even significantly increased especially in the beginning as a sign of a lesion of the upper motor neuron, which also serves in the form of increased mass Terre flexes, the diagnosis. The patients sometimes also show a loss of control when laughing, crying or yawning ( emotional lability ).

An electromyographic and electro euro graphical examination is essential for diagnosis. For the diagnosis of internationally standardized criteria were developed (El - Escorial criteria).

What is important is the distinction between the tropical spastic paraparesis, because this caused by HTLV -1 disease is contagious.

The loss of material is visible at autopsy: it concerns the praecentralen cortex in the cerebrum in which the cell bodies of upper motor neuron are, the anterior horns of the spinal cord, where the cell bodies of lower motor neuron lie, and extending therebetween nerves (called pyramidal tract from the precentral gyrus to the spinal cord ).

Treatment

The treatment of patients with amyotrophic lateral sclerosis occurs ideally in an interdisciplinary team of health and nurses, occupational therapists, physiotherapists, speech therapists, orthopedists, pulmonologists and neurologists, psychologists, and the general practitioner. It includes on the one hand, tackling the problem in the disease mechanism drug therapy with riluzole and the other, the symptomatic therapy oriented. Symptomatic treatment should help to avoid complications of muscular weakness and improve the quality of life of patients.

Neuroprotective therapy

Tackling the problem at the suspected disease mechanism Riluzole is also referred to as neuroprotective therapy, as the drug used to inhibit the destruction of motor neurons. Riluzole is a so-called glutamate antagonist that affects the effect of the neurotransmitter glutamate on the nerve cell. Studies showed that the administration of riluzole caused a prolongation of survival time ( on average about three months). In addition, it is assumed that the patient remain in the early stages of the disease longer. However, the progression of the disease can not be stopped by riluzole.

Symptomatic therapy

The symptoms and complications occurring typically in the course of the disease can be treated by a variety of therapeutic measures. Important areas of symptomatic therapy are dysphagia (and a concomitant flow of saliva from the mouth ), speech problems, seizures, or Tonuserhöhungen the muscles, weakness of the respiratory muscles and psychological changes such as depression or anxiety.

Muscle cramps ( Cramps )

Spasms of individual muscles (eg, calf cramps) are a common, but also non-specific early symptom of ALS. The spasms can also affect several muscles at the same time. You can spontaneously - without apparent immediate reason - or after exercise, cold exposure, sleep deprivation, alcohol or nicotine occur. For acute therapy, passive stretching of the muscle is recommended. To prevent regular physical training, physiotherapy exercises and massages are recommended. With the appropriate distress quinine sulfate, magnesium or carbamazepine can be used.

Swallowing disorder

Due to a weakness of the pharyngeal muscles results in ALS patients to swallow (dysphagia ). Ensures the normal swallowing process that no parts of the ingested food or liquid fall ( saliva) in the airways. An impaired swallowing mechanism increases the risk of so-called aspiration pneumonia - pneumonia caused to the lungs as a result of the crossing of liquids. Furthermore, it can come with frequent ingestion of a weight loss and lack of fluid intake with the risk of dehydration due to the severe food intake. When symptoms occur, a change of diet to pureed food and thickened liquids is recommended. High-calorie dietary supplements may be used to meet the energy needs of the organism. Using speech therapy measures can sip 'll learn techniques that facilitate the patient's swallowing. As with further progression of the disease, these measures often no longer sufficient to ensure the required food and fluid intake, the plant of a feeding tube ( PEG tube ) is recommended. This is to be created in advance, since in patients with advanced respiratory muscle weakness, the complication rate is increased during the installation. The oral food intake is still possible even after installation of a feeding tube.

Salivation

A flow of saliva from the mouth ( drooling ) occurs as a result of dysphagia and weakness of the mouth and neck muscles. In ALS patients there is no increased production of saliva. The sialorrhoea is socially stigmatizing and is often experienced by affected patients as stressful. She is using drugs that inhibit the production of saliva (eg, amitriptyline, scopolamine or glycopyrrolate ) as well as physiotherapy, speech therapy and orthopedic measures (such as training of the lip and losing the support of the neck muscles) very treatable.

Speech disorder and communication

The impairment of tongue, mouth and palate muscle as well as a speaking -related dyspnea in ALS patients lead to a progressive speech disorder ( dysarthria ). The restriction of communication with the environment is experienced by patients and their families as very stressful. A talking therapy ( speech therapy ) treatment at an early stage is therefore appropriate, in which the breathing and speaking should be facilitated and coordinated with the help of exercises. In addition, is also recommended early on a supply of communication aids. Here are, for example alphabet and picture boards to use. Especially computer-based communication aids also enable the development of the disease, the communication with the environment. Special systems can, for example, with the fingers, are controlled in advanced paralysis also using eye movements. Using so-called brain - computer interfaces can transmit brain waves on a computer and made ​​readable.

Pathological laughing and crying

As pathological laughing and crying ( Pseudobulbäraffekt, pseudobulbar emotional lability ) refers to a sudden, the situation inappropriate laughing or crying of the patient. The symptom occurs in up to 50 percent of ALS patients and is organic. If the patient desire amitriptyline therapy or so-called serotonin - reuptake inhibitors such as citalopram or fluvoxamine can be used.

Breathing disorder

In advanced ALS occurs regularly to weakness of the respiratory muscles and thereby a decreased ventilation of the lungs ( hypoventilation ). This reduction in lung function ( respiratory failure ) leads to a reduced oxygen content in the blood ( hypoxemia ) and - due to reduced exhalation - to increased carbon dioxide levels in the blood ( hypercapnia ). Symptoms of disturbed respiratory function are sleep disturbances, morning headaches, daytime sleepiness, difficulty concentrating, restlessness, and in advanced cases, shortness of breath (dyspnea ). By respiratory infections ( such as aspiration pneumonia ) may continue to impair the function of the lungs. The respiratory failure is the major cause of the limited life expectancy in ALS patients.

When symptoms of respiratory failure, there is the possibility of adapting a feasible also in the home mechanical ventilation ( home ventilation ). Differences are known as a non-invasive and invasive ventilation. In the non-invasive ventilation is a mechanically assisted ventilation, which is done via a breathing mask and is mainly nocturnal used over 6 to 8 hours. Noninvasive ventilation can the symptoms of lung dysfunction mitigate and improve the quality of life. In cases of severe respiratory failure is a mechanical ventilation via a tracheostomy ( after surgical tracheotomy ) possible ( NIV ). Both the adaptation of a non-invasive ventilation as well as the installation of a tracheostomy and subsequent mechanical ventilation therapy are options that are at an early stage discussed with the patient. Approximately 15 percent of patients opt for a nocturnal non-invasive ventilation and less than 10 percent for mechanical ventilation via a tracheostomy. The proportion of patients who take a mechanical support of ventilation in claim differs between different cultures, countries and ethnic groups.

Depression, insomnia and anxiety

A depressive syndrome with depression, sadness and drive reduction can considerably reduce the quality of life of the patient. Depressive episodes can be treated with psychotherapy, both medically with antidepressants such as amitriptyline, sertraline, fluoxetine or paroxetine. For the treatment of sleep disorders sleep hygiene measures and zolpidem and diphenhydramine are used. For sleep disorders that occur in the context of a depressive episode, an additional antidepressant therapy takes place. Anxiety may occur, for example in shortness of breath. In addition to treating underlying causes lying can - with appropriate distress - are used medication diazepam, lorazepam or bupropion.