Defenisi

ALS (amyotrophic lateral sclerosis) merupakan penyakit yang terutama pada system saraf
yang mengantur gerakan motorik yang disadari. Amyotrophic berasal dari kata yunani yang
berarti tidak adanya nutrisi terhadap otot yang berarti berkurang/hilangnya signal dari sel saraf
ke sel otot. Lateral berarti samping merujuk pada lokasi kerusakan pada spinal cord. Sclerosis
berart penebalan yang berarti penebalan pda spinal cord pada ALS. ALS merupakan penyakit
saraf progresif yang serius yang menyebabkan kelemahan otot, kecacatan, dan akhirnya
kematian. ALS juga disebut sebagai penyakit Lou Gehrig, yang meruapakn nama dari seorang
pemain baseball yang meninggal pada tahun 1941 karena penyakit tersebut.. ALS juga disebut
sebagau motor neuron disease. (FACTS als)
Motor neuron disease (MND) merupakan kelompok gangguan neudegeneratif dengan
karakteristik hilangnya neurons pada motor cortex, batang otak, dan serabut anterior spinal cord.
Manifestasi klinik tergantung pada keterlibatan upper motor neuron -UMN (kelemahan,
kekakuan, hiperrefleks) atau lower motor neuron LMN (kelemahan, menurun/hilangnya reflex
fisiologis, fasikulasi). Chacot (1874) menggambarkan adanya gejalan LMN dan UMN pada
penderita ALS. MND dapat melibatkan bagian atas dan bawah limb, sesuai persarafan oleh
nervus bulbar. Survival penderita MND sangat rendah, kematian biasanya terjadi 3-5 tahun
setelah munculnya gejala, kematian banyak disebabkan oleh gangguan respirasi. (02)

Epidemiologi

Population based studies have established that the incidence of ALS in Europe is fairly uniform

at 216 per 100 000 person years. Although ALS affects people worldwide, an exact incidence

of this disease is not yet known. Men have a higher incidence of disease (30 per 100 000

person-years; 95% CI 2833) than do women (24 per 100 000 personyears; 95% CI 222

6), although the incidence between men and women is about the same in familial disease. The
overall population-based lifetime risk of ALS is 1:400 for women and 1:350 for men. Peak age at
onset is 5863 years for sporadic disease and 4752 years for familial disease. Incidence
decreases rapidly after 80 years of age. (PII)
Studi berbasis populasi telah menetapkan bahwa kejadian ALS di Eropa cukup seragam pada 2-
16/100.000 orang tiap tahun. Meskipun ALS mempengaruhi seluruh populasi dunia, kejadian penyakit
ini pastinya belum diketahui. Pria memiliki insidensi penyakit yang lebih tinggi (300/100 000 orang tiap
tahun) dibandingkan wanita (2-4/100 000 orang tiap tahun), meskipun kejadian antara pria dan wanita
hampir sama dalam penyakit keluarga. Risiko seumur hidup berbasis populasi keseluruhan ALS adalah 1:
400 untuk wanita dan 1: 350 untuk pria. Usia puncak saat onset adalah 58-63 tahun untuk penyakit
sporadis dan 47-52 tahun untuk penyakit familial. Insiden menurun dengan cepat setelah usia 80 tahun

Gejala klinis dan diagnosis

ALS leads to progressive degeneration of the motor neurons that supply voluntary muscles. The
disease affects LMNs in the medulla and anterior horn of the spinal cord as well as UMNs in the
cerebral cortex. The result for patients is progressive muscle weakness leading to death, usually
from respiratory failure. The median survival time after diagnosis is approximately 6 months for
25 % of patients, 12 months for 25 % and more than 18 months in the remainder.20 This
variability makes anticipating survival time difficult. Limb-onset symptoms, younger age, better
motor function, higher breathing capacity, stable weight and longer interval between symptom
onset and diagnosis are all associated with longer survival.

Clinical features of muscles wasting in a patient with ALS

Proximal and symmetrical upper limb wasting (A) results in an inability to lift arms against
gravity (man-in-the barrel or flail-arm variant ALS). Note the recessions above and below the
scapular spine (B), indicating wasting of supraspinatus and infraspinatus muscles, as well as
substantial loss of deltoid muscle. As a consequence, the glenohumeral joint becomes prominent,
and prone to subluxation. (C) Disproportionate wasting of the thenar muscles combined with the
first dorsal interossei, the so-called split-hand, is a typical feature in ALS.17 Although the
mechanisms underlying this disproportionate wasting of hand muscles are unclear, a
corticomotoneuronal origin has been proposed.17 Specifically, the thenar muscles and first
dorsal interossei receive more extensive corticospinal connections and thereby might be prone to
glutamate-mediated excitotoxicity.18 (D) Substantial wasting of the tongue muscles in bulbar-
onset ALS. Note the absence of palatal elevation present on vocalisation. Difficulty with mouth
opening and dysphagia might require supplementary feeding through a percutaneous endoscopic
gastrostomy. In further support of a corticomotoneuronal hypothesis, the tongue is often
disproportionately aff ected in comparison to other oropharyngeal musculature in patients with
bulbar-onset ALS. As with the thenar muscles in the hand, the tongue receives more extensive
cortical input than other muscle groups in the oropharyngeal area.

Degeneration of LMNs causes fasciculation, cramps, muscle atrophy and marked weakness,
which is often more problematic for patients than the spasticity, hyper-reflexia and modest
weakness associated with loss of UMNs. Babinski and Hoffmann signs, along with emotional
lability are also typical of UMN degeneration. ALS begins in the limbs in about two-thirds of
patients, most often in the arms. The first symptoms are usually unilateral and focal. Early
findings include foot drop, difficulty walking, loss of hand dexterity or difficulty lifting the arms
over the head. Eventually, limb function can be lost, leading to dependence on caregivers.
Patients may fall or lose the ability to walk all-together. Bulbar-onset disease, often occurring in
older women, appears to have worse prognosis.22 Dysarthria usually begins before dysphagia;
symptoms may progress to anarthria, drooling and malnutrition. An atrophied fasciculating
tongue is so characteristic of bulbar ALS that it is virtually diagnostic of the condition. Axial
weakness can cause dropped head and kyphosis, features associated with pain and poor balance.
Sphincter and sensory functions are usually spared. Eye movements are preserved until advanced
stages. Cognitive impairment in ALS was first described by Pierre Marie in the 19th Century,23
but the association was considered uncommon until recently. Overt frontotemporal dementia
occurs in approximately 15 % of patients, but as many as 50 % are impaired by
neuropsychological tests.24,25 Changes involve language, judgment, personality, affect and
executive function. Patients with ALS and dementia have shorter survival, possibly as a result of
poor decision-making ability.26 Depression and anxiety can occur during any stage, from
diagnosis to the time of respiratory failure, though patients suffering from ALS often approach
the disease philosophically and rates of depression may be lower than expected.27 When present,
emotional symptoms impair quality of life through poor appetite and sleep, and feelings of
hopelessness. Pain can sometimes result from degeneration of sensory neurons, and more
commonly from contractures, loss of mobility, inability to turn in bed, or bedsores. The suffering
from being unable to move can be extreme.28 Morning headache, weakened cough, orthopnoea
and exertional dyspnea are early respiratory symptoms. Later, shortness of breath develops, first
during simple tasks such as dressing and eating, and eventually at rest. (8gordon)

The diagnosis depends on progressive UNM and LMN findings by history and examination.
Diagnosing ALS remains difficult because of the lack of a reference test with a high positive
predictive value. In 1994 a set of diagnostic criteria, the El Escorial criteria, was put forward by
the World Federation of Neurology. These criteria primarily rely on clinical symptoms and the
exclusion of other disorders. The El Escorial criteria were based on the consensus between the
members of the Research Group on Motor Neuron Disease (ALS) and additional clinicians and
researchers involved in ALS research (Table 1.1). The aim of these diagnostic criteria was not
primarily meant to be used in clinical practice, but to enhance clinical research, therapeutic trials
and molecular genetic studies. To increase the sensitivity of these diagnostic criteria, they have
been revised in 2000 (revised El Escorial criteria)88 and 2006 (Awaji algorithm). (proefs)
Pada tahun 1994 dibuat kriteria diagnostik, kriteria El Escorial, yang diajukan oleh Federasi Neurologi
Dunia. Kriteria ini terutama bergantung pada gejala klinis dan menyingkirkan gangguan lainnya. Tujuan
kriteria diagnostik ini tidak hanya untuk digunakan dalam praktik klinis, namun juga untuk
meningkatkan penelitian klinis, percobaan terapeutik dan studi genetika molekuler. Untuk
meningkatkan sensitivitas kriteria diagnostik ini, mereka telah dilakukan revisi pada tahun 2000 (kriteria
El Escorial yang telah direvisi) dan pada tahun 2006 (algoritma Awaji).
Electromyography confirms widespread LMN disease and excludes other conditions such as
multifocal motor neuropathy with conduction block. Brain and spinal MRI exclude conditions
that affect the UMN such as cervical spondylosis. Occasionally the brain MRI shows bilateral
signal changes in the corticospinal tracts, a finding that is pathognomonic of ALS. Blood tests to
exclude disorders that mimic ALS also are conducted. In some instances, a muscle biopsy, which
involves taking a small sample of muscle under local anesthesia, is performed.