Pendahuluan

Amyotrophic lateral sclerosis (ALS) is the most common degenerative disease of

the motor neuron system. The disorder is named for its underlying
pathophysiology, with amyotrophy referring to the atrophy of muscle fibers,
which are denervated as their corresponding anterior horn cells degenerate.
Lateral sclerosis refers to the changes seen in the lateral columns of the spinal
cord as upper motor neuron (UMN) axons in these areas degenerate and are
replaced by fibrous astrocytes (gliosis).
ALS is a fatal disease, with a median survival period of 3 years from onset of
weakness.[4] (See Prognosis.) Aspiration pneumonia and medical complications of
immobility contribute to morbidity in patients with the disease.
ALS was first described in 1869 by the French neurologist Jean-Martin Charcot
and hence is also known as Charcot disease; however, it gained popular
recognition and its best-known eponym in the United States after the baseball
player Lou Gehrig announced his diagnosis with the disease in 1939.[5, 6, 7, 8, 9] ALS
is also known as motor neuron disease (MND).
The cause of ALS is unknown, although a family history of the disease is obtained
in about 5% of patients, and twin studies show a genetic contribution with
heritability of about 61%.[10] In some

cases, ALS

overlaps

clinically,

pathologically, and biologically with frontotemporal dementia, and it may share

common biologic mechanisms with Alzheimer disease, Parkinson disease, and
other neurodegenerative diseases.[11, 12, 13, 14] (See Etiology.)
Degenerative effects of ALS
ALS is one of the system degeneration diseases, disorders that cause networks
that work together in health to disintegrate together in an organized manner.[15,
16]

ALS results from the systematic dismantling of the motor neuron system, with

the clinical manifestations in each patient deriving from the site of onset and cell
type involved; the relative affinity of the dismantling process for prefrontal, upper
and lower motor neurons; and the rate of the diseases spread within the network.
[17]

In its classic form, ALS affects motor neurons at 2 or more levels of the motor
neuron network supplying multiple regions of the body. It affects lower motor
neurons (LMNs) that reside in the anterior horn of the spinal cord and in the brain
stem, corticospinal UMNs that reside in the precentral gyrus, and, frequently,
prefrontal motor neurons that are involved in planning or orchestrating the work
of the upper and lower motor neurons.[18] (See Pathophysiology.)
Loss of LMNs leads to progressive muscle weakness, wasting (atrophy), and
fasciculations, with loss of reflexes and muscle tone. Loss of corticospinal UMNs
usually leads to milder weakness associated with stiffness (spasticity), which may
be severe, and abnormally brisk reflexes.
Loss of prefrontal neurons may result in special forms of cognitive impairment
that include, most commonly, executive dysfunction but that may also include an
altered awareness of social implications of ones circumstances and, consequently,
maladaptive social behaviors.[19] In its fully expressed forms, the prefrontal
dysfunction meets established criteria for frontotemporal dementia.[20,

21]

Loss of

ability to integrate motor function (apraxia), a premotor function, is seen at times.

It is more noticeable in limbs that are not overly weak.
Types of motor neuron disease
Classic ALS
The term classic ALS is reserved for the form of disease that involves upper and
lower motor neurons. The classic form of sporadic ALS usually starts as
dysfunction or weakness in one part of the body and spreads gradually within that
part and then to the rest of the body.[22] Ventilatory failure results in death 3 years,
on average, after the onset of focal weakness. The rate of disease progression
varies widely, however, with some patients dying a few months after experiencing
their first symptom and others still walking 10 years afterward.

Progressive muscular atrophy and flail limb syndrome

The disease may be restricted to LMNs. When the pattern of LMN involvement is
asymmetrical, the disorder is termed progressive muscular atrophy (PMA), and
the course is usually indistinguishable from that of classic ALS. Patients with a
symmetrical pattern, called flail limb syndrome, have a course that may be far
longer.[23]
Primary lateral sclerosis
When only UMNs are involved, the disease is called primary lateral
sclerosis (PLS). The course of PLS differs from that of ALS and is usually
measured in decades.[24]
Progressive bulbar palsy
Rarely, the disease is restricted to bulbar muscles, in which case it is called
progressive bulbar palsy (PBP). In most patients who present with initial
involvement of bulbar muscles, the disease evolves to classic ALS.
Familial ALS
Worldwide, a family history of ALS is obtained in about 5% of cases; these
patients have familial ALS. Most familial ALS is inherited in an autosomal
dominant pattern,[18] often with reduced penetrance, but other patterns, such as Xlinked or autosomal recessive inheritance, are seen (see Etiology.)
The fact that in most patients ALS is sporadic does not preclude a genetic
contribution to the disease in these cases. ALS as a whole is best thought of as a
disease showing complex inheritance.
Complications
Complications of ALS can include the following:

Progressive inability to perform activities of daily living (ADLs),

including handling utensils for self feeding

Deterioration of ambulation

Aspiration pneumonia

Respiratory insufficiency

Complications from being wheelchair-bound or bedridden, including

decubitus ulcers and skin infections (while rare in patients with ALS, these
complications can emerge if appropriate padding is not used)

Deep vein thromboses and pulmonary emboli (these are rare in patients
with ALS, but have been encountered with greater frequency in the active
treatment arm of some clinical trials)
Diagnosis and treatment
The diagnosis of ALS is primarily clinical. Electrodiagnostic testing contributes to
the diagnostic accuracy (see Clinical Presentation and Workup). Making a
diagnosis is important to patients and families, allowing them to stop the search
for alternative causes of a patient's disability and to focus their attention on
treatment.
Although ALS is incurable, there are treatments that can extend the length and
meaningful quality of life for patients (see Treatment).
Mechanism-specific treatments directed at the processes that cause the disease to
evolve after it has expressed itself sufficiently to be diagnosed may, at best, have
an ameliorative effect. Treatments that halt the spread of the disease may be more
effective than those that try to salvage affected motor neurons. All of these have
yet to be realized. Currently, the mainstay of ALS therapy is adaptive treatments
directed at the clinical manifestations of the disease.