|Year : 2010 | Volume
| Issue : 2 | Page : 45-50
Amyotrophic lateral sclerosis
VS Gulecha, MS Mahajan, RA Khandare, HH Gangurde, Aman Upaganlawar, CD Upasani
S.S.D.J. College of Pharmacy, Neminagar, Chandwad, - 423 101, (M.S.), India
|Date of Web Publication||24-Mar-2011|
V S Gulecha
S.S.D.J. College of Pharmacy, Neminagar, Chandwad, MS - 423 101
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder with no effective treatment. It occurs when specific nerve cells in the brain and spinal cord that control voluntary movement gradually deteriorate. The loss of these so-called motor neurons causes the muscles under their control to weaken and waste away, leading to paralysis. ALS varies from patient to patient, depending on which muscles weaken first. ALS strikes in mid-life and it is observed that men are about one-and-a-half times more likely to have the disease as women. The present review is an attempt to give an insight into the signs, symptoms, diagnosis and symptomatic treatment of ALS.
Keywords: Amyotrophic lateral sclerosis, Lou Gehrig′s disease, neurodegenerative disorder
|How to cite this article:|
Gulecha V S, Mahajan M S, Khandare R A, Gangurde H H, Upaganlawar A, Upasani C D. Amyotrophic lateral sclerosis. Ann Nigerian Med 2010;4:45-50
|How to cite this URL:|
Gulecha V S, Mahajan M S, Khandare R A, Gangurde H H, Upaganlawar A, Upasani C D. Amyotrophic lateral sclerosis. Ann Nigerian Med [serial online] 2010 [cited 2020 Oct 24];4:45-50. Available from: https://www.anmjournal.com/text.asp?2010/4/2/45/78270
| Introduction|| |
Amyotrophic lateral sclerosis (ALS, sometimes called Maladie de Charcot) is a progressive, usually fatal, neurodegenerative disease caused by the degeneration of motor neurons, the nerve cells in the central nervous system that control voluntary muscle movement. This condition is often referred to as Lou Gehrig's disease in the USA. The disorder causes muscle weakness and atrophy throughout the body as both the upper and lower motor neurons degenerate, ceasing to send messages to upper and lower muscles. Unable to function, the muscles gradually weaken, and develop twitches because of denervation. The patient may ultimately lose the ability to initiate and control all the voluntary movements, bladder and bowel sphincters and the muscles responsible for eye movement are usually (but not always) spared. 
Many people are uncomfortable with the profound physical changes of a disease that generally leaves a person mentally intact. The patient is often very distressed over diminishing quality of life, which raises ethical issues regarding aggressiveness of treatment, ventilation, no cardiopulmonary resuscitation (CPR) orders and assisted suicide. The patient experiences multiple losses such as that of mobility, speech, the ability to eat and drink, and independence. The patient may also experience loss of some relationships and personal fulfillment. The frustration and loss of control may lead to anxiety, anger, depression and controlling behavior. Up to 50% of ALS patients have pseudobulbar effect, pathological uncontrolled bouts of laughing or crying not concordant with their mood. ,,, Four recent epidemiologic studies have reported an association between development of ALS and prior service in the US military. Three of those studies ,, evaluated veterans of the 1991 Persian Gulf War; the fourth  evaluated veterans who served in the military in the period 1910-1982.
| Prevalence|| |
There are about 1-3 cases per 100,000 per year, and 50% survival rates range from 36 to 48 months [95% confidence interval (CI)] after the onset of symptoms has been seen. 
| Epidemiology|| |
ALS is mainly associated with motor neurons that link nervous system with voluntary muscle of the body. In ALS, these motor neurons degenerate which results in malfunctioning of neurons, causing the muscle to weaken gradually or may lead to atrophy and muscle twitching. Eventually, the ability of the brain to start and control voluntary movement is lost. 
Familial ALS (fALS) accounts for approximately 5-10% of all ALS cases and is caused by genetic factors. Of these, approximately 1 in 10 is linked to a mutation in copper/zinc superoxide dismutase 1 (Cu/Zn SOD1), an enzyme responsible for scavenging free radicals. A recent study has identified a gene called FUS ("Fused in Sarcoma", ALS6) as being responsible for 1 in 20 cases of fALS. , Historically ALS had a high incidence (as much as 143 cases per 100,000 people per year) of a condition called Lytico-Bodig disease which is a combination of ALS, Parkinsonism More Details, and dementia. 
| Etiology|| |
The cause of ALS is not known, but mutations in the gene that produces the Cu/Zn SOD1 enzyme have been associated with some cases (approximately 20%) of fALS. Most of the current literature suggests the involvement of Cu/Zn SOD1 in the pathogenesis of fALS.  This enzyme is a powerful antioxidant that protects the body from damage caused by superoxide, a toxic free radical. Free radicals can accumulate and cause damage to DNA and proteins within cells. Although it is not yet clear how the SOD1 gene mutation leads to motor neuron degeneration, researchers have theorized that an accumulation of free radicals may result from the faulty functioning of this gene. ,
| Pathophysiology|| |
Skeletal muscles are innervated by a group of neurons (lower motor neurons) 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 neurons that project from the motor cortex of the brain. On macroscopic pathology, it is found that 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. On microscopic examination, neurons may show spongiosis, the presence of astrocytes, and a number of inclusions including characteristic "skein-like" inclusions, Bunina bodies, and vacuolization. 
| Causes and Risk Factors|| |
Definitive causes for ALS have not yet been found, but the onset of the disease has been linked to several factors including a virus, exposure to neurotoxins or heavy metals, DNA defects, immune system abnormalities, and enzyme abnormalities. Surgeries involving the spinal cord have also been thought to play a role in the onset of ALS due to the disruption of nerve fibers. There is a known hereditary factor in fALS; however, there is no known hereditary component in the 90-95% cases diagnosed as sporadic ALS. An inherited genetic defect on chromosome 21 is associated with approximately 20% of fALS. ,
| Symptoms|| |
The onset of ALS may be so elusive that the symptoms are frequently overlooked. The earliest symptoms may include twitching, cramping, or stiffness of muscles; muscle weakness affecting an arm or a leg; slurred and nasal speech; or difficulty chewing or swallowing. These general complaints then develop into more obvious weakness or atrophy. 
The symptoms of ALS vary from one person to another but the majority of people experience the following:
- Muscle weakness in arms or legs
- Clumsy hand - dropping/fumbling with items
- A hoarse voice
- Shoulder dysfunction
- Weak foot-foot drop and difficulty walking
- Exercise intolerance, abnormal fatigue and
- Muscle cramps or twitches
Death usually results from the complications of inactivity or from paralysis of the muscles that control breathing. ,
| Diagnosis|| |
The ALS can be diagnosed by electromyography (EMG), a special recording technique that detects electrical activity in muscles. Another common test measures nerve conduction velocity (NCV). Specific abnormalities in the NCV results may suggest, for example, that the patient has a form of stacking and gowning neuropathy or myopathy (muscle disease) rather than ALS. The other tests include magnetic resonance imaging (MRI), a noninvasive procedure that uses a magnetic field and radio waves to take detailed images of the brain and spinal cord. Although these MRI scans are often normal in patients with ALS, they can reveal evidence of other problems that may be causing the symptoms, such as a spinal cord tumor, multiple sclerosis, a herniated disk in the neck, syringomyelia, or cervical spondylosis.
Infectious diseases such as human immunodeficiency virus (HIV), human T-cell leukemia virus (HTLV), Lyme disease,  syphilis,  and tick-borne encephalitis  viruses can in some cases cause ALS-like symptoms. Neurological disorders such as multiple sclerosis, post-polio syndrome, multifocal motor neuropathy and spinal muscular atrophy also can mimic certain facets of the disease and should be considered to make a diagnosis.
| Differential Diagnosis|| |
The possibility of other motor deficit diseases (e.g. myasthenia, motor conduction block neuropathy, cervical syringomyelia) should be eliminated as they can resemble ALS in its early stages.
Because ALS is a progressive disease, the patient's condition, needs, and those of careers should be assessed regularly, if possible within the home. By assessing deficits and how they affect what the patient can do, the course of the handicap and deterioration in vital functions can be anticipated. For maximum efficacy, assessments should be coordinated by ALS centers that can provide a multidisciplinary consultation at a single site.
Initial tests, repeated every 3 months
- Interview: Situation with regard to family, work, social life, home environment, etc.
- Disability: ALS Functional Rating Scale (ALSFRS-R), [functional independence measure (FIM), Barthel index]
- Walking range, pain
- Manual muscle testing
- Speech therapy assessment: Dysarthria, swallowing, communication
- Psychological assessment
- Nutritional status: Weight, height, body mass index (BMI), dietary habits
- Respiratory function
- Signs of sleep disorders, dyspnea, orthopnea, bronchial congestion
- Vital capacity, peak expiratory flow (PEF) with cough test, maximal inspiratory pressure (PI max), sniff nasal inspiratory pressure (SNIP), nocturnal oximetry (every 6 months), blood gas analysis (at the outset, then according to disease progression).
Genetic tests should be ordered only in cases of fALS (at least two family members affected irrespective of the degree of relationship) or if the phenotype is atypical. ,
| Treatment|| |
No cure has been found yet. However, the Food and Drug Administration has approved the first drug treatment for the disease: Riluzole (Rilutek). It acts by preventing damage to motor neurons by decreasing the release of glutamate via activation of glutamate transporters and also by its neuroprotective effects, by means of sodium and calcium channel blockades,  inhibition of protein kinase C  and the promotion of N-methyl d-aspartate (NMDA) receptor antagonism.  Clinical trials with ALS patients showed that Riluzole lengthens survival by several months, and may have a greater survival benefit for those with a bulbar onset. The drug also extends the time before a patient needs ventilation support. Riluzole does not reverse the damage already done to motor neurons, and patients taking the drug must be monitored for liver damage and other possible side effects. 
| Emergency Department Care|| |
Management by a multidisciplinary team
Management should be coordinated, flexible, and adjusted for the patient's stage of deficit by a professional team [physiotherapist, occupational therapist, speech therapist, nurse, nursing auxiliary, home help, medical and personal support assistant, social worker, psychologist, dietician, beautician, careers (family, volunteers), service providers]. Each team member helps the patient cope as much as possible with their handicap under the conditions of greatest comfort. 
Symptomatic drug therapies
Non-specific symptoms: Fatigue, depression and anxiety, constipation, pain, cramp. There are no ALS-specific drugs for these symptoms. Conventional treatment should be given in accordance with good clinical practice.
Specific symptoms are symptoms requiring special treatment because they occur in a patient with ALS.
- Stasis: Tricyclics, scopolamine, botulin toxin A or radiotherapy
- Change in consistency of saliva: Beta-blockers
- Nighttime dry mouth combined with daytime stasis: Difficult to treat
- Spasticity: Baclofen, tizanidine, dantrolene or benzodiazepines
- Emotional lability: Tricyclics or serotonin reuptake inhibitors
- Sleep disorders: Look for respiratory problems and for anxiety and/or depression
- Antihistamines or hypnotics: Avoid benzodiazepine derivatives if possible.
| Life Support|| |
Palliative care should be discussed well before it is likely to be needed if the patient seems to be willing to participate. The patient's wishes should be complied with in this respect. Whatever the patient's decision early on during the course of the disease, they should be able to request and benefit from palliative care at any time.
Enteral feeding prevents the effects of malnutrition, improves patient comfort and may prolong survival. It should be given via a percutaneous endoscopic gastrostomy tube. The clinical criteria for starting enteral feeding are feeding problems.
Respiratory assistance - either non-invasive ventilation (NIV) using a mask or tracheotomy - should be given at home. It is clear that it improves comfort, sleep and survival, but it does not stop the disease progression. It should be started when the patient has symptoms of alveolar hypoventilation.
Acute respiratory failure
In the event of acute respiratory failure, the decision to provide ventilation (NIV or intubation), palliative care, or sedation during the terminal stage should be taken after considering factors in the patient's history, any wishes expressed by the patient, his or her personal and family history, and any uncertainty about whether or not the acute respiratory failure is reversible. When deciding on the best form of care, the patient's comfort and support for the patient and careers are taken into consideration. ,
| Drugs in the Management of ALS|| |
A growing body of research suggests that ALS, especially the hereditary type that appears at younger age, is associated with a defect in SOD, an enzyme of the antioxidant system, in which the SOD produced by the body changes from an antioxidant (that is protective to nerves) to a pro-oxidant that damages the nerves. Thus, antioxidant therapies might help slow the progression of the disease, at least in individuals with this genetic defect. The possibility of beneficial effects from antioxidants has been proposed, but has not been confirmed. Indeed, many people with ALS turn to taking nutritional supplements rich in antioxidants but do not report significant improvements; formal studies have yet to be undertaken.
Herbal therapies for ALS are aimed at nourishing the kidney to benefit the marrow and spinal cord, and at vitalizing blood to soften the sclerosis and invigorate the circulation to the affected muscles. The traditional formula most often mentioned for treatment of wasting syndrome is Huqian Wan (Hidden Tiger Pill), which is sometimes modified by adding additional tonic herbs. A key herb in this formula is tortoise shell, which is used for flaccidity and debility, especially of the lower limbs. However, the basis for the design of Huqian Wan is the concept that a heat-type disease damages the yin fluid, leading to the atrophy of muscles. For this reason, Huqian Wan contains rehmannia, tortoise shell, and peony to nourish and retain the yin essence, and anemarrhena and phellodendron to quell the deficiency fire of the kidney that threatens the remaining yin. Although this mechanism may apply to some cases of ALS, there is no clear evidence that a heat-type syndrome precedes its development or that yin deficiency heat dominates the syndrome.
A formula Yisui Tang (Boost the Marrow Decoction) used for progressive spinal myodystrophies, including ALS is similarly formulated; it is made with tortoise shell, deer antler gelatin, rehmannia, dipsacus, cuscuta, atractylodes, licorice, astragalus, psoralea, cibotium, achyranthes, tang-kuei, peony, millettia, phellodendron, and anemarrhena. This combination, given as a decoction with 9-15 g of each ingredient (except only 5 g each of phellodendron and anemarrhena), was used to treat 110 patients, of whom 30 were diagnosed as having ALS. , Preclinical data indicate that Cannabis has powerful antioxidative, anti-inflammatory, and neuroprotective effects. In the G93A-SOD1 ALS mouse, this has translated to prolonged neuronal cell survival, delayed onset, and slower progression of the disease. Cannabis also has properties applicable to symptom management of ALS, including analgesia, muscle relaxation, bronchodilation, saliva reduction, appetite stimulation, and sleep induction.  Vitamin C, calcium, magnesium, vitamins B, E and creatine have been shown to treat patients with ALS. 
| Conclusion|| |
It can be concluded from the information furnished above that no cure has been yet found for ALS. However, the Food and Drug Administration has approved the first drug Riluzole (Rilutek) for the treatment. Other treatments for ALS relieve the symptoms and improve the patient's quality of life. To provide effective treatment for ALS, a healthcare professionals' team including doctors, pharmacist, therapist, social worker and home care specialist should work together.
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