Charishma et al, J. Global Trends Pharm Sci, 2018; 9(1): 4880 - 4885
An Elsevier Indexed Journal ISSN-2230-7346
Journal of Global Trends in Pharmaceutical Sciences
AMYOTROPHIC LATERAL SCLEROSIS – A PROGRESSIVE MUSCLE WEAKNESS S.Charishma*,D.Eswar Tony, Rama Rao Nadendla
Department of Pharmacy Practice Chalapathi Institute of Pharmaceutical Sciences, Guntur, Andhra Pradesh 522 034
*Corresponding author E-mail: [email protected] ARTICLE INFO ABSTRACT Key words Amyotrophic lateral sclerosis (ALS) is a nervous system disease that attacks nerve cells called neurons in your brain and spinal cord. The Amyotrophic lateral neurons transmit messages from your brain and spinal cord to your sclerosis, voluntary muscles. At first, this ALS causes mild muscle problems and Lou Gehrig’s disease later people suffering with ALS may find trouble in walking, running, Neurodegenerative writing and also problems in speech. When muscles in chest fail, people disorder, multiple cannot breathe and most of the people die with ALS due to respiratory sclerosis. failure. The disease usually strikes between ages 40 to 60 and there is no cure as medicines relieve symptoms and sometimes prolong survival. In the followed review article, we highlighted the etiology, diagnosis, management and disease modifying treatment in this article and moreover as the reasons for ALS are not exactly confirmed, extensive research is required to find out the causes behind this progressive muscle weakness. INTRODUCTION Amyotrophic lateral sclerosis causes await discovery. Once the disease (ALS) ALS is a disease that leads to begins, a number of processes transpire in progressivedegeneration of motor system– both neurons and surrounding glial cells; Hallmark is involvement of both upper and how these processes interact is an area of lowermotor neurons. It is characterised by active research.As in progressive degeneration of upper (UMN) otherneurodegenerative diseases, a and lower (LMN) motor neurons in the prominent event in damaged neurons brain and spinal cord. Rare in its own isaggregation of misfolded protein, which right, ALS is the most common form of might influence nearby wild typeprotein to motor neuron disease (MND).ALS is change conformation and in this way, almost as mysterious today as it was in the explain how a diseasethat begins in one first part of the 20th Century. There are no area is transmitted widely in the brain. known causes for most patients and no Incidence of ALS is 2-3 people per 100 cures. Genetic mutations account for some 000 most commondegenerative disorder of of the 5–10 % of cases that are inherited the motoneuronal system inadults. (familial ALS [fALS]), usually in a Caucasian peoplewere more frequently Mendelian trait. Sporadic ALS (sALS) is affected than other ethnicgroups. thought to have both genetic and According to gender men were effected environmental influences, but the principle more than women (1.2-1.5:1).Risk of this
4880
Charishma et al, J. Global Trends Pharm Sci, 2018; 9(1): 4880 - 4885 condition is peak between the ages of 50- upper motor neuron (UMN)disease: 75 years, then declines. Both sporadic and Spasticity, Weakness, Increased reflexes, inherited forms of the disease, among them Normal muscle bulk and for lower motor 10% due to inherited gene mutations. The neuron (LMN)disease: Muscle wasting, ALS cases can be classified into Weakness, Fasciculations, Dropped sporadic,familial, and from the western reflexes. Pacific(ALS and Parkinsonism-Dementia Diagnosis Complex),the later very common in Diagnosis is done after 14 months Chamorro people ofGuam and Marianas from onset of symptoms until diagnosis is island, the Kii peninsulaof Honshu Island, initial broaddifferential diagnosis: Based and the Auyu and Jakai peopleof south primarily on clinical exam: west New Guinea. In around 5-10%there is No definitive diagnostic test evidence of family history (familialALS), may involve: and, approximately 20% of these Laboratory testing variantsare linked to the gene encoding the Electromyography enzymecopper-zinc superoxide dismutase (fasciculation, denervation (Cu-ZnSOD1), and 2-5% have mutations discharges, polyphasic units) of TARDBP(TDP-43) gene. Genetic testing
Etiology Neuroimaging (MRI) Currently unknown that might be El Escorial criteria in 1994 geographic and occupationalClusters or (World Federation of environmental factors. It can be also Neurology) occurs by the following mechanisms such Multiplerevisions as Mitochondrial dysfunction, Protein Definite diagnosis requires: aggregation, Free radical generation, LMN degeneration on clinical, Excitotoxicity, Inflammation and electrophysiological, or apoptosis, Multifactorial and contributions neuropathological exam from multiple genes andenvironmental UMN degeneration on clinical exposures. ALS leads to progressive exam degeneration of the motor neurons that Progression of motor syndrome supplyvoluntary muscles. The disease within a region or to other affects LMNs in the medulla and regions anteriorhorn of the spinal cord as well as Absence of evidence of other UMNs in the cerebral cortex. The resultfor disease processes that may patients is progressive muscle weakness explain the symptoms leading to death, usually fromrespiratory There are different criteria for the failure. The median survival time after identification of the type of the ALS, diagnosis is approximately6 months for 25 among them El Escorial and Awaji-Shima % of patients, 12 months for 25 % and criteria which improved the diagnostic more than 18months in the remainder.This criteria without false reports. Several variability makes anticipating survival investigations are included in diagnosing timedifficult. Limb-onset symptoms, the ALS: younger age, better motor function, higherbreathing capacity, stable weight All patients in whom ALS is suspected and longer interval between symptomonset CBC, Calcium, Phosphate, and diagnosis are all associated with PTH, TSH, liver enzymes longer survival. Generally both the upper Nerve conduction studies/EMG and lower motor neurons are effected and represents different features such as for MRI of most affected regions
4881
Charishma et al, J. Global Trends Pharm Sci, 2018; 9(1): 4880 - 4885
If predominantly UMN pattern complications(level B) and improve quality of life (level C). MRI brain and c-spine +/- other levels 2. The following specialists should be Copper and zinc levels part of or readilyavailable to the multidisciplinary clinic team: If predominantly LMN pattern neurologist,respiratory physician, gastroenterologist, Anti-GM1 antibodies rehabilitationmedicine physician, Vasculitis/inflammatory social counsellor,occupational serology therapist, speech therapist, Lead/mercury levels respiratorytherapist, specialized West Nile serology nurse, physical therapist, Kennedy’s genetic testing (if dietitian,psychologist, dentist and bulbar predominant, male) palliative care physician(GCPP). Spinal muscular atrophy genetic testing (if shoulder/hip 3. Patients should generally be girdle) reviewed every2–3 months, although they may require more The following tumours can lead to frequentreview in the months aparaneoplastic motor neuron disease following diagnosis or in the laterstages of disease, and less Non-Hodgkin’s lymphoma frequent review if their diseaseis Hodgkin’s lymphoma progressing slowly. The patient Small cell lung cancer support teamshould maintain Testicular germ cell tumour regular contact with the patient Renal cell carcinoma andrelatives between visits Breast (GCPP). Ovarian 4. Ideally, the patient should be Screening followed by the sameneurologist liaising closely with the patient is CT chest/abdo/pelvis primarycare physician (family Testicular U/S, mammography general practitioner) (GCPP). Management 5. Effective channels of There is no cure yet for ALS, so communication and co- care is aimed at maintaining quality oflife ordinationare essential between and prolonging life as much as possible. the hospital-based The current foundationsare a single multidisciplinaryclinic team, the neuroprotective medication, primary healthcare sector,the multidisciplinary clinics andventilatory palliative care team and support. Some therapies can help relieve community services(GCPP). symptoms. And also there are some recommendations such as: Neuroprotective treatment/disease- modifying treatment 1. Multidisciplinary care should be available for peopleaffected by To date, Riluzole is the only drug ALS. Attendance at that has been shown toslow the course of multidisciplinary clinicsmay ALS. Oraladministration of 100 mg extend survival, decrease medical riluzole daily improved the1-year survival by 15% and prolonged survival by 3
4882
Charishma et al, J. Global Trends Pharm Sci, 2018; 9(1): 4880 - 4885 months after 18 months of treatment. • Keppra (levetiracetam) may be There was aclear dose effect. Eleven beneficial– 500mg po bid up to 1000mg po people needed to be treatedwith riluzole to bid delay one death for 12 months. • Cannabinoids ineffective Symptomatic treatment • Non pharmacologic (no trials)– Exercise, Sialorrhoea in ALS was treated physiotherapy, massage, hydrotherapy with amitriptyline, oral ortransdermal hyoscine, or sublingual atropine Spasticity: Pharmacologic– Baclofen, drops(GCPP). Maximum 80 mg daily, in divided doses 1. In patients with refractory • Consider intrathecal pump if intractable– sialorrhoea, botulinumtoxin Tizanidine, Maximum 24mg daily, in injections into the parotid and/or divided doses submandibulargland are effective • Non-pharmacologic– Physiotherapy and generally well tolerated (level Bfor botulinum toxin type B, level • Mainstay of treatment C for type A toxin). • Shown to be effective– Hydrotherapy, 2. Irradiation of the salivary glands Heat, cold therapy may be tried whenpharmacological treatment fails (GCPP). Venous Thrombosis: Increased risk of DVT – 2.7% annual incidence– 3. Surgical interventions are not Immobility, Impaired respiratory function recommended (GCPP). and No studies to guide management and also Current practice– Insufficient Bronchial Secretions evidence to recommend prophylaxis, Difficulty clearing secretions Anticoagulate if DVT common complaint Nutritional support: The consequences No controlled trials in ALS of malnutrition in patients with ALS are Options to consider well known. Inadequate dietaryintake can exacerbate catabolism and atrophy of Mucolytic agent: N-acetylcysteine 200- respiratory muscles, weaken the 400mg tid and only use if patient is able to immunesystem and contribute to infection. cough effectively Weight loss and below-normal body mass index(BMI) resulting from deficient Anti cholinergic bronchodilator: energy intake among ALS patients are Ipratropium correlated with shortened survival. Several Beta-blocker: Metoprolol or propranolol more recent studies confirm the observation that weight loss (and / Humidifier: Portable suction device ormalnutrition), defined as BMI ≤ 18.5kg/m2, is an independent, negative, Cramps: Common complaint, can be prognostic indicatorfor survival. troublesome at night “Neutraceuticals”, “functional foods” and “dietary supplements” are terms used to • Quinine– Banned by FDA, Cochrane describechemical components of foods that review, No greater AEs compared with may display unique, disease-fighting placebo pharmacokinetics andpharmacodynamics • BeneficialDose 200 mg bid when ingested in amounts above that of one’s typical diet.
4883
Charishma et al, J. Global Trends Pharm Sci, 2018; 9(1): 4880 - 4885
Fig.1 Etiology of Amylotrophic Lateral Sclerosis (ALS)
Criteria Definite ALS Probable ALS Possible ALS Suspected ALS El Escorial Upper and lower Upper and lower motor Upper and lower Lower motor motor neuron neuron signs motor neuron neuron signs in 3 regions in at least 2 regions, in 1 region, upper signs only, in 2 with upper motor motor alone in 2 or more regions signs, lower motor regions, or lower neuron signs rostral to motor neuron signs lower motor neurons rostral to lower motor neurons
Awaji-Shima Clinical or Clinical or Clinical or NA electrophysiological electrophysiological electrophysilogical evidence, evidence, signs of upper and demonstrated by the demonstrated by the lower motor neuron prescence of upper prescence of upper and dysfunction in only and lower motor lower motor neuron 1 region, or upper neuron signs in the signs in the bulbar motor neuron signs bulbar region and at region and at least 2 alone in 2 or more least 2 spinal spinal regions, with regions, or lower regions, or the some upper motor motor neuron signs presence of upper neuron signs rostral to upper and lower motor necessarily rostral to motor neuron signs. neuron signs in 3 the lower motor spinal regions. neuron signs.
Theemergence of neutraceutical use within Coenzyme Q10, Alpha-Lipoic acid, L- the patient population has defined a Cartine, Glutathione, Herbs growing andsubstantial treatment modality. Commonly used dietary Functional supports: Red Wine,
supplements are: Vitamin A, Vitamin B6, Epigallocatechin gallate. Zinc, Genistein, Melatonin, Creatinine,
4884
Charishma et al, J. Global Trends Pharm Sci, 2018; 9(1): 4880 - 4885
REFERENCES 1. Derghazarian, Amyotrophic Lateral Sclerosis A Clinical Overview, 2004, palliative care of neurology. 2. M Andersena, S Abrahamsb, G D Borasioc, M d Carvalhod, A Chioe, P V Dammef et.al; The EFNS Task Force on Diagnosis and Management of Amyotrophic Lateral Sclerosis , 2012, European Journal of Neurology, 19: 360– 375. 3. Punter, the Palliation of Amyotrophic Lateral Sclerosis, 2013. 4. C Coupe and P H Gordon, Amyotrophic Lateral Sclerosis – Clinical Features, Pathophysiology and Management, 2013, European neurological review, 8(1):38–44 5. J Rosenfeld and A Ellis, Nutrition and Dietary Supplements in Motor Neuron Disease, Phys Med RehabilClin N Am. 2008 August ; 19(3): 573- 587.
4885