2 Motor Neurone Disease (ALS) This Article is dedicate to my close Friend Mr.Ayoob, Ex Production Manager, California Gardens,Dubai, Who is now suffering from this very rare disease. Now he is in Hospital with serious condition. There is no cure for this Disease. Allah(The Most merciful) only will cure him. Please pray for him. Er.Sulthan
3 Medical Hand Book -5A From Er.Sulthan Hello Doctor!Medical Hand Book -5AFrom Er.Sulthan
4 குலசை சுல்தான் வழங்கும் மருத்துவ கையேடு-5A (ENGLISH) ஹலோ டாக்டர்!குலசை சுல்தான்வழங்கும்மருத்துவ கையேடு-5A(ENGLISH)
5 Health Manager Motor Neurone Disease ( ALS) Presentation From Er.Sulthan
6 ALS is a progressive neurodegenerative disease that kills one in 1,000 adult Canadians. Most die within five years of their first symptom.There is no cure for ALSCurrently there is no cure for ALS. The only drug that affects the course of the disease is riluzole. The drug functions by blocking the effects of the neurotransmitter glutamate, and is thought to extend the lifespan of an ALS patient by only a few months.
7 The rate that the disease progresses varies from person to person The rate that the disease progresses varies from person to person. Muscles weakened by ALS-MND do not recover. However, weeks or months may go by where the disease does not seem to progress. Eventually, severe disability develops. As the disease becomes severe, people with ALS-MND are unable to walk, talk or eat, and need a lot of care. The outlook for people with ALS-MND is variable. About 7 in 10 people with ALS-MND die within 3-5 years of the onset of symptoms. About 2 in 10 survive five years, and about 1 in 10 survives 10 years or more.
9 The motor neurone diseases (or motor neuron diseases) (MND) are a group of neurological disorders that selectively affect motor neurones, the cells that control voluntary muscle activity including speaking, walking, breathing, swallowing and general movement of the body.What are Motor Neuron Diseases?The motor neuron diseases (MNDs) are a group of progressive neurological disorders that destroy cells that control essential muscle activity such as speaking, walking, breathing, and swallowing. Normally, messages from nerve cells in the brain (called upper motor neurons) are transmitted to nerve cells in the brain stem and spinal cord (called lower motor neurons) and from them to particular muscles. When there are disruptions in these signals, the result can be gradual muscle weakening, wasting away, and uncontrollable twitching (called fasciculations). Eventually, the ability to control voluntary movement can be lost. MNDs may be inherited or acquired, and they occur in all age groups. In adults, symptoms often appear after age 40. In children, particularly in inherited or familial forms of the disease, symptoms can be present at birth or appear before the child learns to walk.
10 The causes of sporadic (noninherited) MNDs are not known, but environmental, toxic, viral, or genetic factors may be implicated. Common MNDs include amyotrophic lateral sclerosis (ALS), progressive bulbar palsy, primary lateral sclerosis, and progressive muscular atrophy. Other MNDs include the many inherited forms of spinal muscular atrophy and post-polio syndrome, a condition that can strike polio survivors decades after their recovery from poliomyelitis.Is there any treatment?There is no cure or standard treatment for the MNDs. Symptomatic and supportive treatment can help patients be more comfortable while maintaining their quality of life. The drug riluzole (Rilutek®), which as of this date is the only drug approved by the U.S. Food and Drug Administration to treat ALS, prolongs life by 2-3 months but does not relieve symptoms. Other medicines that may help reduce symptoms include muscle relaxants such as baclofen, tizanidine, and the benzodiazepines for spasticity; glycopyrrolate and atropine to reduce the flow of saliva; quinine or phenytoin for cramps; anticonvulsants and nonsteroidal anti-inflammatory drugs to relieve pain; tranquilizers to help with sleeping problems; antidepressants; and botulinum toxin, amitriptyline, and other anticholinergic drugs to control drooling. Some patients may require stronger medicines such as morphine to cope with musculoskeletal abnormalities or pain in later stages of the disorders, and opiates are used to provide comfort care in terminal stages of the disease.
11 Physical and speech therapy, occupational therapy, and rehabilitation may help to improve posture, prevent joint immobility, slow muscle weakness and atrophy, and cope with swallowing difficulties. Applying heat may relieve muscle pain. Assistive devices such as supports or braces, orthotics, speech synthesizers, and wheelchairs help some patients retain independence.What is the prognosis?Prognosis varies depending on the type of MND and the age of onset. Some MNDs, such as primary lateral sclerosis, are not fatal and progress slowly. Patients with spinal muscular atrophy may appear to be stable for long periods, but improvement should not be expected. Some MNDs, such as ALS and some forms of spinal muscular atrophy, are fatal.What research is being done?The National Institute of Neurological Disorders and Stroke (NINDS) conducts research related to the MNDs in its laboratories at the National Institutes of Health (NIH), and also supports additional research through grants to major medical institutions across the country. Much of this research focuses on finding better ways to prevent, treat, and ultimately cure disorders such as the MNDs.
12 TerminologyIn this article, MND refers to a group of diseases that affect motor neurones. In the United States, MND is more commonly called Amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, after the baseball player. In France the disease is sometimes known as Maladie de Charcot (Charcot's disease), although it may also be referred to by the direct translation of ALS, Sclerose Laterale Amyotrophique (SLA). To avoid confusion, the annual scientific research conference dedicated to the study of MND is called the International ALS/MND Symposium.
14 HistoryAlthough other 19th century neurologists previously described the disease, a French neurologist, Jean-Martin Charcot, first suggested grouping together disparate conditions that affect the lateral horn of the spinal cord in 1869.ClassificationForms of motor neurone disease include:• amyotrophic lateral sclerosis (ALS) (sometimes called Lou Gehrig's disease)• primary lateral sclerosis (PLS)• progressive muscular atrophy (PMA)• bulbaro pseudobulbar palsy - spastico progressive bulbar palsy - spastic and flaccidSpinal muscular atrophy (SMA) is classified under MND by MeSH, but not by ICD-10.
15 Symptoms of motor neurone disease The symptoms of motor neurone disease (MND) usually follow a pattern that is marked by three stages:• the initial stage,• the advanced stage, and• the end stage.
16 Initial symptomsThe initial symptoms of MND usually develop slowly and subtly over time. It can be easy to mistake early symptoms for those of a number of unrelated neurological conditions (conditions affecting the nervous system).The initial symptoms of MND may include:• a weakened grip, which can make it difficult to pick up or hold objects,• a general feeling of tiredness,• muscle pains and cramps,• muscle twitches,• slurred speech,• weakness in the arms and/or legs, and• a feeling that you have become much more clumsy than usual, such as always tripping over.
17 Advanced symptomsThe advanced symptoms of MND are outlined below.Muscle weaknessIf you have MND, your limbs will become progressively weaker, and the muscles in your limbs will begin to shrink. As a result of this, you will find it increasingly difficult to move your affected limbs.Muscle spasmsThe twitching in your muscles will also get worse, and it is likely that you will experience muscle spasms (twinges). You may also notice that certain muscles in your limbs become unusually stiff. This type of muscle stiffness is known as spasticity.PainThe combination of muscle spasms and stiffness can lead to episodes of pain in your muscles and joints.Difficulty swallowingIf you have MND, you will find it increasingly difficult to swallow, which may make eating and drinking problematic. Difficulty swallowing is known as dysphagia.
18 Excessive droolingIf you have MND, you may find that you have problems controlling the production of saliva and that you experience excessive and/or constant drooling of watery saliva.Excessive yawningSome people with MND find that they experience episodes of uncontrollable, excessive yawning, even when they are not tired. This can sometimes cause jaw pain.Difficulty talkingAs MND progresses, you may find it increasingly difficult to control the muscles of your throat and mouth, making it difficult for you to talk.Emotional changesMND does not usually affect a person’s intelligence, but it can lead to changes in a person’s personality and emotional state.One of the most common signs of this is known as emotional lability. Emotional lability is when a person experiences episodes of uncontrollable crying or laughter.There is often no connection between these episodes and a person’s actual emotional state or their immediate environment. For example, someone with emotional lability may break into uncontrollable laughter when watching a news report about a serious incident, such as an air crash.
19 Cognitive changes and dementia Occasionally, people with MND may experience difficulties with memory, learning, language and concentration. This is known as cognitive change. Some of these changes may be quite subtle, making it difficult to tell them apart from the normal ageing process.A small number of people with MND may also be diagnosed with dementia at some time. It is important that help and advice is sought from healthcare professionals who are trained in the treatment of MND and dementia.
20 Cognitive changes and dementia Occasionally, people with MND may experience difficulties with memory, learning, language and concentration. This is known as cognitive change. Some of these changes may be quite subtle, making it difficult to tell them apart from the normal ageing process.A small number of people with MND may also be diagnosed with dementia at some time. It is important that help and advice is sought from healthcare professionals who are trained in the treatment of MND and dementia.
21 Breathing difficulties As the nerves and muscles that help control your lungs become progressively more damaged, you will find that your breathing becomes increasingly difficult.This usually develops as a feeling of being very short of breath after carrying out everyday tasks, such as walking up the stairs. Over time, you may become very short of breath, even when you are resting.This shortness of breath may be particularly troublesome at night. Some people find it difficult to breathe when they are lying down, while others find themselves waking suddenly in the night as a result of breathlessness.As MND progresses, it is likely that you will need mechanical assistance with your breathing - for example, you may need to use an oxygen mask.
22 End-stage symptomsAs MND progresses to its final phase, it is likely that you will experience:total body paralysis, andsignificant breathing difficulties.Eventually, mechanical assistance, such as using an oxygen mask, will not be enough to compensate for the loss of normal lung function. At this stage, most people with MND become increasingly drowsy before falling into a deep sleep. They usually die peacefully in their sleep.Secondary symptomsA number of people with MND will experience additional symptoms that are not directly caused by the condition, but are related to the stress and anxiety of living with MND.These secondary symptoms include:depression,insomnia, andanxiety.
23 CausesAbout 90% of cases of MND are "sporadic", meaning that the patient has no family history of ALS and the case appears to have occurred with no known cause. Genetic factors are suspected to be important in determining an individual's susceptibility to disease, and there is some weak evidence to suggest that onset can be "triggered" by as yet unknown environmental factors (see 'Epidemiology' below).Approximately 10% of cases are "familial MND", defined either by a family history of MND or by testing positive for a known genetic mutation associated with the disease. The following genes are known to be linked to ALS: Cu/Zn superoxide dismutase SOD1, ALS2, NEFH (a small number of cases), senataxin (SETX) and vesicle associated protein B (VAPB).
24 Of these, SOD1 mutations account for some 20% of familial MND cases Of these, SOD1 mutations account for some 20% of familial MND cases. The SOD1 gene codes for the enzyme superoxide dismutase, a free radical scavenger that reduces the oxidative stress of cells throughout the body. So far over 100 different mutations in the SOD1 gene have been found, all of which cause some form of ALS(ALSOD database). In North America, the most commonly occurring mutation is known as A4V and occurs in up to 50% of SOD1 cases. In people of Scandinavian extraction there is a relatively benign mutation called D90A which is associated with a slow progression. In Japan, the H46R mutation is most common. G93A, the mutation used to generate the first animal model (and by far the most widely studied), is present only in a few families worldwide. Future research is concentrating on identifying new genetic mutations and the clinical syndrome associated with them. Familial MND may also confer a higher risk of developing cognitive changes such as frontotemporal dementia or executive dysfunction (see 'extra-motor change in MND' below).
25 It is thought that SOD1 mutations confer a toxic gain, rather than a loss, of function to the enzyme. SOD1 mutations may increase the propensity for the enzyme to form protein aggregates which are toxic to nerve cells.PathophysiologySkeletal muscles are innervated by a group of neurones (lower motor neurones) located in the ventral horns of the spinal cord which project out the ventral roots to the muscle cells. These nerve cells are themselves innervated by the corticospinal tract or upper motor neurones that project from the motor cortex of the brain. On macroscopic pathology, there is a degeneration of the ventral horns of the spinal cord, as well as atrophy of the ventral roots. In the brain, atrophy may be present in the frontal and temporal lobes.
26 On microscopic examination, neurones may show spongiosis, the presence of astrocytes, and a number of inclusions including characteristic "skein-like" inclusions, bunina bodies, and vacuolisation.The availability of mouse models has led to extensive research into the causes of SOD1-mutant linked familial ALS. The most commonly used mouse model is G93A , although many others have since been generated. At the gross physiological level, the mouse models faithfully recapitulate the features of human ALS (motorneuron death, muscle atrophy, respiratory failure).
27 Although there is no consensus as to the exact mechanism by which mutated SOD1 causes the disease (in either mice or patients), studies based largely on mouse models suggest a role for excitotoxicity and more controversially, oxidative stress, presumably secondary to mitochondrial dysfunction. Death by apoptosis has also been suggested.Signs and symptomsSymptoms usually present themselves between the ages of 50-70, and include progressive weakness, muscle wasting, and muscle fasciculations, spasticity or stiffness in the arms and legs, and overactive tendon reflexes. Patients may present with symptoms as diverse as a dragging foot, unilateral muscle wasting in the hands, or slurred speech.Neurological examination presents specific signs associated with upper and lower motor neurone degeneration. Signs of upper motor neurone damage include spasticity, brisk reflexes and the Babinski sign. Signs of lower motor neurone damage include weakness and muscle atrophy.Note that every muscle group in the body requires both upper and lower motor neurones to function. The signs described above can occur in any muscle group, including the arms, legs, torso, and bulbar region.
28 The symptoms described above may resemble a number of other rare diseases, known as "MND Mimic Disorders". These include, but are not limited to, multifocal motor neuropathy, Kennedy's disease, hereditary spastic paraplegia, spinal muscular atrophy and monomelic amyotrophy. A small subset of familial MND cases occur in children, such as "juvenile ALS", Madras syndrome, and individuals who have inherited the ALS2 gene. However, these are not typically referred to as MND, but by their specific names.
29 DiagnosisThe diagnosis of MND is a clinical one, established by a neurologist on the basis of history and neurological examination. There is no diagnostic test for MND. Investigations such as blood tests, electromyography (EMG), magnetic resonance imaging (MRI), and sometimes genetic testing are useful to rule out other disorders that may mimic MND. However, the diagnosis of MND remains a clinical one. Having excluded other diseases, a relatively rapid progression of symptoms is a strong diagnostic factor. Although an individual's progression may sometimes "plateau", it will not improve.A set of diagnostic criteria called the El Escorial criteria have been defined by the World Federation of Neurologists for use in research, particularly as inclusion/exclusion criteria for clinical trials. Owing to a lack of clinical diagnostic criteria, some neurologists use the El Escorial criteria during the diagnostic process, although strictly speaking this is functionality creep, and some have questioned the appropriateness of the criteria in a clinical setting.
30 TreatmentCurrently there is no cure for ALS. The only drug that affects the course of the disease is riluzole. The drug functions by blocking the effects of the neurotransmitter glutamate, and is thought to extend the lifespan of an ALS patient by only a few months.The lack of effective medications to slow the progression of ALS does not mean that patients with ALS cannot be medically cared for. Instead, treatment of patients with ALS focuses on the relief of symptoms associated with the disease. This involves a variety of health professionals including neurologists, speech-language pathologists, physical therapists, occupational therapists, dieticians, respiratory therapists, social workers, palliative care specialists, specialist nurses and psychologists.
31 PrognosisMost cases of MND progress quite quickly, with noticeable decline occurring over the course of months. Although symptoms may present in one region, they will typically spread. If restricted to one side of the body they are more likely to progress to the same region on the other side of the body before progressing to a new region. After several years, most patients require help to carry out activities of daily living such as self care, feeding, and transportation.MND is typically fatal within 2–5 years. Around 50% die within 14 months of diagnosis. The remaining 50% will not necessarily die within the next 14 months as the distribution is significantly skewed. As a rough estimate, 1 in 5 patients survive for 5 years, and 1 in 10 patients survive 10 years. Professor Stephen Hawking is a well-known example of a person with MND, and has lived for more than 40 years with the disease.Mortality normally results when control of the diaphragm is impaired and the ability to breathe is lost. One exception is PLS, which may last for upwards of 25 years. Given the typical age of onset, this effectively leaves most PLS patients with a normal life span. PLS can progress to ALS, decades later.
32 ComplicationsEmotional labilityMain article: labile affectAround a third of all MND patients experience labile affect, also known as emotional lability, pseudobulbar affect, or pathological laughter and crying. Patients with pseudobulbar palsy are particularly likely to be affected, as are patients with PLS.Extra-motor changeCognitive change occurs in between 33–50% of patients. A small proportion exhibit a form of frontotemporal dementia characterised by behavioural abnormalities such as disinhibition, apathy, and personality changes. A small proportion of patients may also suffer from an aphasia, which causes difficulty in naming specific objects. A larger proportion (up to 50%) suffer from a milder version of cognitive change which primarily affects what is known as executive function. Briefly, this is the ability of an individual to initiate, inhibit, sustain, and switch attention and is involved in the organisation of complex tasks down to smaller components. Often patients with such changes find themselves unable to do the family finances or drive a car. Depression is surprisingly rare in MND (around 5–20%) relative to the frequency with which it is found in other, less severe, neurological disorders e.g. ~50% in multiple sclerosis and Parkinson's disease, ~20% in Epilepsy. Depression does not necessarily increase as the symptoms progress, and in fact many patients report being happy with their quality of life despite profound disability. This may reflect the use of coping strategies such as reevaluating what is important in life.
33 Although traditionally thought only to affect the motor system, sensory abnormalities are not necessarily absent, with some patients finding altered sensation to touch and heat, found in around 10% of patients. Patients with a predominantly upper motor neurone syndrome, and particularly PLS, often report an enhanced startle reflex to loud noises.Neuroimaging and neuropathology has demonstrated extra-motor changes in the frontal lobes including the inferior frontal gyrus, superior frontal gyrus, anterior cingulate cortex, and superior temporal gyrus. The degree of pathology in these areas has been directly related to the degree of cognitive change experienced by the patient, if any. Patients with MND and dementia have been shown to exhibit marked frontotemporal lobe atrophy as revealed by MRI or SPECT neuroimaging.
35 EpidemiologyThe incidence of MND is approximately 1–5 out of 100,000 people. Men have a slightly higher incidence rate than women. Approximately 5,600 cases are diagnosed in the U.S. every year. By far the greatest risk factor is age, with symptoms typically presenting between the ages of Cases under the age of 50 years are called "young onset MND", whilst incidence rates appear to tail off after the age of 85.Tentative environmental risk factors identified so far include: exposure to severe electrical shock leading to coma, having served in the first Gulf War, and playing Association football (soccer). However, these findings have not been firmly identified and more research is needed.
36 Research effortsThe search for a drug that will slow MND progression is under way. Agents that are currently in trials include ceftriaxone, arimoclomol, IGF-1, lithium  and coenzyme Q10 to name but a few.EtymologyTerminology around the motor neurone diseases can be confusing; in the UK "motor neurone disease" refers to both ALS specifically (the most common form of disease) and to the broader spectrum of motor neurone diseases including progressive muscular atrophy, primary lateral sclerosis, and progressive bulbar palsy. In the United States the most common terms used are ALS (both specifically for ALS and as a blanket term) or "Lou Gehrig's disease".Amyotrophic comes from the Greek language: A- means "no", myo refers to "muscle", and trophic means "nourishment"; amyotrophic therefore means "no muscle nourishment," which describes the characteristic atrophication of the sufferer's disused muscle tissue. Lateral identifies the areas in a person's spinal cord where portions of the nerve cells that are affected are located. As this area degenerates it leads to scarring or hardening ("sclerosis") in the region.
37 ALS/MOTOR NEURON DISEASE A VERY IMPORTANT DISCOVERY ALS/MOTOR NEURON DISEASE A VERY IMPORTANT DISCOVERY! Remember, there is no definitive test to prove the diagnosis of ALS, except an autopsy. Generally the diagnosis is made by trying to eliminate other neuromuscular degenerate diseases and then waiting. But the longer one waits the more evident it becomes that a singular out-come will be produced! It is like the Beltway around Washington, DC, one can exit on to many different roadways, each with a different name. But though some routes are longer than others, they all lead to the same place!Regardless of which of the above titles is used, as time passes by the determining factor will be the accumulation of symptoms. Don't be negative and assume that everything you hear about ALS is necessarily true in your case. Don't concentrate your thoughts on negatives and dying, concentrate your thoughts on living each day that you have to the fullest.Some ALS patients live 10, 15, 20 30, or more years. Some even recover! There are no guarantees in life about anything, but isn't it better to make the most of each day?According to research reported by the Mayo Clinic, patients with long duration illness have the same disease as those with short duration illness. Also, Mayo Clinic investigators were impressed, that at autopsy the long duration patient's neuropathologic findings were much the same as those found in patients who had died earlier in the course of their illness.During a physical examination of 100 consecutive patients at the Mayo Clinic it was found five years from onset of illness that fully 20% of the patients were living. Ten years from onset almost 10% were living, and in this particular study 2 patients lived for 18 years.
38 Several patients whom the Mayo Clinic diagnosed as having ALS subsequently recovered. It was the Mayo Clinic's experience that the more benign "course" of ALS could be differentiated readily from patients who demonstrated a number of etiologies for muscular atrophy that superficially resembled motor neuron disease.There is some good news for those who have Spinal Bulbar Muscular Atrophy, and there is some very bad news. The good news is that it generally progresses much more slowly than other forms of Motor Neuron/ALS. The bad news is that it is familiar, or inherited.
39 We Pray For Your Good Health Action is the proper fruit of knowledge.The best of all medicines is resting and fastingHealth is a blessing that money cannot buy.From Er.SulthanE