BAB I

INTRODUCTION

1.1 Background

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that

causes severe muscle weakness, disability, and eventually lead to death due to the
degeneration of motor neurons in the primary motor cortex, brain stem and
Medulla spinalis. ALS was first described in 1869 by Jean-Martin Charcot a
French neurologist and hence also known as Charcot disease, but gained popular
acclaim and the most famous of his eponymous after baseball player Lou Gehrig
Announces diagnosis with the disease in 1939. ALS, also known as motor neuron
disease (MND). 1
Amyotrophic lateral sclerosis (ALS) is a term used for a neurodegenerative
syndrome characterized by progressive degeneration of motor neurone. However,
ALS is a term used in modern clinical practice to show the most common form of
the disease, classical (Charcot) ALS. Other syndromes associated with motor
neuron degeneration include Progressive bulbar, cerebral (PBP), Progressive
muscular atrophy (PMA), primary lateral sclerosis (PLS), Flail arm syndrome
(Vulpian-Bern-Hardt syndrome), Flail (Pseudopolyneuritic legs syndrome form)
and ALS with a multi-user system involvement (e.g., ALS-Dementia). Lord
Russell proposed Motor Brain term. 2
Genesis (an average of 1.89 per 100,000/year) and prevalence (average 5.2
per100, 000) are relatively uniform in Western countries, although the focus of
higher frequency occur in the Western Pacific. The average age of onset for
sporadic ALS is about 60 years. Overall, there is a slight male prevalence (M: F
ratio of 1.5:1). 3
The cause of ALS is unknown, although 5-10% of cases are familial. Some
research suggests that ALS can have the same biological mechanism of
Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases. In
the classical form, ALS affects motor neuron in 2 or more levels that innervate the

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multiple areas of the body. This affects the lower motor neurons located in the
anterior cornu of the spinal cord and the brain stem, jaras kortikospinalis upper
motor neuron located in the precentral gyrus, gyrus prefrontal motor neuron and is
often involved in planning activities upper and lower motor neurons. 1
In this disease the arrangement of somatosensory altogether is not
interrupted. Thus, its manifestation consists of movement disorder, who showed
signs of UMN paralysis and LMN simultaneously. Therefore, hiperefleksia,
klonus and pathological reflex can be found side by side with muscle atrophy and
arefleksia on a single sufferer. 3
The classic form of ALS sporadic usually begins as a dysfunction or
weakness in one part of the body and spread gradually in the body and then to the
rest of the body. The deaths were discovered due to the failure of ventilation, an
average of 3 years after the onset of focal weakness. If only lower motor neurons
are involved, this disease called progressive muscular atrophy (PMA). When only
the upper motor neurons are involved, this disease called amyotrophic lateral
primer (PLS). 1
The diagnosis of ALS is primarily clinically. Electrodiagnostic testing
contributes to the accuracy of diagnostic. ALS is a fatal disease, with an average
survival of 3-5 years. Aspiration pneumonia and medical complications of
immobility contribute to morbidity in patients with ALS. Although ALS is not
curable, there are treatments that can extend quality of life, so the diagnosis is
important to patients and families. 1

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 CHAPTER II
A REVIEW OF THE LITERATURE

A. Anatomy and Physiology

1. Upper motor neuron 4
All the neurons that transmit motor impulses to the LMN group belongs to the
UMN. Based on the physiological and anatomical differences UMN group is
divided in the order of pyramidal and ekstrapiramidal.
a. Pyramidal arrangement 4
All the neurons that transmit motor impulses directly to the LMN or via
interneuronnya, belongs to the Group of the UMN. Neurons are the residents of
girus presentralis. Therefore, it is called girus then the motor cortex. They were on
the path to-V and each has a relationship with a particular muscle motion. That
was in the motor cortex which overlooks the longitudinalis serebri has connection
with the motion of the muscles of the feet and lower limbs. The motor cortex
neurons close to the lateral fissure serebri take care of motion of muscles of the
larynx, farings and tongue. The investigation by elektrostimulasi revealed that the
motion of the muscles all over the body can be mapped on the whole area of the
motor cortex contralateral side. Map it is known with the motor homunculus.
From the mesial girus presentralis (= 4 = area of the motor cortex) to the
lateral portion of the bottom, respectively, there is a map of the movement of the
legs, upper limb, lower limb, hip, abdominal/thoracic, shoulders, arms, hands,
neck, fingers, face, lips, muscles of the vocal cords, the tongue and muscles
penelan. That caught my attention is the extent of the area of the map movement
and limited area-specific agile movement of the common swift. Through the
aksonya the motor cortex neurons contact the motorneuron forms the core of the
motor cranial nerve and the anterior kornu motoneuron in the medulla spinalis.
The axons Askon-compile kortikobulbar-kortikospinal jaras. As the nerves of
their compact beam down from the motor cortex and thalamus and in the level of
their basal ganglia between both buildings. That is what is called internal kapsula,
which can be divided into anterior and posterior Crucible crucibles. The angle

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formed the second part was known as the internal genu. The arrangement of
somatotopik that have been found in the motor cortex was found back in the area
range from the internal genu kapsula until the entire area a crucible posterius. At
the level of mesensefalon fibers-fibers that are gathered in the central part of the
3/5 pedunkulus serebri and flanked by regions of frontopontin-wire, fibers from
the medial side and parietotemporopontin-wire, fibers from the lateral side. In the
pons the fibers-fibers above occupied pes pontis, there are core-core diamana
place wire-wire frontopontin and parietotemporopontin ends. Thus, the building
which is a continuation of pes fibers contain only pontis-wire kortikobulbar and
kortikospinal only. Banguna piramis and was known as the ventral medulla
oblongata is a part.
Throughout the brainstem, wire-wire, kortikobulbar leave their area (in
pedunkulus serebri, then in the pes pontis, and finally in piramis), for crossed the
midline and ends directly at the motoneuron motor cranial nerve (n. . III, n. IV, n.
v., VII, n. n.VI, n. IX, n. X, XI and n. n. XII) or contralateral side
interneuronnyadi. Some of kortikobulbar fibers ends in cranial nerve nuclei
Agenesis-side motor as well. On the border between the medulla oblongata and
medulla spinalis, wire-wire, kortikospinal most of the crosses and form the lateral
kortikospinal jaras (= traktus lateral piramidalis), running on funikulus
posterolateralis kontralateralis . Most of them are not crossed but went on a trip to
the medulla spinalis in funikulus ventralis Agenesis and is known as kortikospinal
traktus or ventral jaras piramidalis ventralis. The area of the lateral and ventral
piramidalis jaras makin to kaudal fewer, as many fibers have already ended the
trip. On the servikal delivered 55% of kortikospinal fibers, whereas in parts of
torakal and lumbosakral in a row got 20% and 25%. The majority of the
motoneuron motor impulses are received in the cervical and lumbar intumesensia,
which takes care of the muscles of the upper and lower limbs.
b. Order ekstrapiramidal 4
The order ekstrapiramidal comprises components, namely: the corpus
striatum, globus palidus, talamik nuclei, subtalamikus nucleus, substantia nigra,
formatio retikularis brainstem, cerebellum follows with the motor cortex

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additional areas 4.6 and 8. These components are connected with each other by
the axons of each component of it. Thus there is a circular path, known as the
circuit. Corpus striatum is therefore the sole recipient of the wire-wire all the
neocortex, then called striatal circuit circuit path. Simply put, the trajectory of the
circuit can be distinguished in the striatal circuit main (principal) and 3 supporting
striatal circuit (asesorik). The arrangement is integrated in the motor and sensory
composition, so that it has a system of input and output. Data from the outside
world in the striatal circuit is mainly non-specific asenden impulses are
channelled through diffuse ascending reticular system or track spinotalamik
multisinaptik and proprioseptik impulses received by the cerebellum. The purpose
of the first lap was intralaminares nuclei talami. The data received by the
cerebellum is delivered to the thalamus as well (via brakium konyungtivum). The
nucleus of the thalamus that receives it is lateral nucleus ventralis ventralis
anterior nucleus and talami talami. The second path that data eksteroseptif known
as input circuit striatal system. Striatal circuit output system is a path to transmit
impulses to the striatal circuit processing results motoneuron. The impulse that
has been processed in striatal circuit are sent to area 4 and 6 through globus
palidus and talamik nuclei and striatal messages were delivered to the nucleus
ruber, formation retikularis to finally addressed to the motoneuron. Axons-
dendrites from neurons of layer V of the cortex area of the brain stem down to 4
on jaras frontopontin and to the nucleus ruber and nerve cells in formation
retikularis. Rubrospinal fibers-fibers to contact either the alpha or gamma
motoneuron residing in cervical intumesensia only. While wire-wire,
retikulopinal, most of which is multisinaptik, so the more appropriate nickname
fibres retikulo-spino-spinal, headed to Alpha and gamma motoneuron part
medulla spinalis below the level servikal. At the level of kornu there is a gamma
loop circuit anterius namely neuronal relationship that circle of Alpha motoneuron
muscle pindle-gamma/Alpha motoneuron. Through the system gamma loop that
muscle tone adapted to the agile movement patterns as desired.
I. LOWER MOTONEURON 4

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 Neurons that transmit motor impulses on the last trip to the skeletal muscle
cell is called lower motor neurons (LMN), to distinguish it from UMN. Thus
LMN with aksonnya named by Sherrington "final common path" motor impulses.
LMN concoct nerve brain nuclei and motor nuclei of the spinal nerve radiks
ventralis. Two types of LMN can be distinguished. The first is called α-
motoneuron. He is large and thick aksonnya stick to ekstrafusal fibers. The other
is known as γ-motoneuron, its size is small, sleek and aksonnya mensarafi muscle
fibers intrafusal. With the intercession of both kinds of motoneuron motor
impulses, it can drive the balance of muscle tone required to embody every move
deftly. Each stick is only one motoneuron axons. But in the end each Axon
branches. And every branch of the mensarafi a piece of muscle fibers, and thus
each Axon can be associated with muscle fibers .
A motoneuron with a number of muscle fibers it supplies is one motor or
motor unit of the Union (= motor unit). The task of motoneuron menggalakan
only cells of the muscle fibers so that muscle motion occurred. Motorneuron-
motorneuron only works as mere subordinates implementers. If they are freed
from the influence of the pyramidal system and ekstrapiramidal, then they can still
menggalakan cells of muscle fibers, but the pattern of muscle movement occurs
not in accordance with the will and moreover its nature is not agile. Muscle
movement is reflektorik and rude as well as the massif. When going on a damage
to the motoneuron, then the muscle fibers-fibers that is incorporated in the unit
motoriknya cannot contract, kendatipun the motor impulses can still be delivered
by pyramidal system and ekstrapiramidal to his goal.

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 B. Amyotrophic lateral sclerosis (ALS)
2.1. Definition
Amyotrophic Lateral Sclerosis (ALS) is a disease of the motor neurons that
affect nerve cells of skeletal muscle. A neural network carries messages from the
brain down the spinal cord and out to different parts of the body. Included in this
network is a motor neuron that carries messages to the skeletal muscles. The
ability of nerve cells in ALS progressively reduced and eventually die. As a result,
skeletal muscle nerve signals do not accept that they need to function properly and
atrophy of the muscles gradually due to lack of use and complete. 5
ALS neurodegenerative disorder can be defined as characterized by
progressive muscular paralysis reflecting degeneration of MNS in the primary
motor cortex, brain stem, and spinal cord. "Amyotrophy" refers to the muscle
fiber atrophy, causing muscle weakness exposed and fasikulasi. "Lateral
Sclerosis" refers to hardening of kortikospinalis anterior and lateral channels as
MNS in declining areas of functionality and replaced by gliosis. 6
Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder that causes
weakness, atrophy, paralysis, and eventual respiratory failure due to selective
degeneration of neurons responsible for movement of volunter. 7
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease,
a progressive neuromuscular disease that is caused by damage to the nerve cells in
the brain and spinal cord. This causes loss of control nerves of muscles volunter,
so the muscle atrophy and degeneration. Finally the respiratory muscles are
affected causing death of the inability to breath. 8

2.2. Epidemiology
All of about 5,600 people in the United States are diagnosed with ALS each
year. Events of the year was 2-3 per 100,000 residents, it is 5 times higher than
Huntington's disease and the same with multiple sclerosis. It is estimated that as
many as 16,000 Americans may have the disease at the time of a particular
decade. The incidence of ALS is higher in men than in women, with the ratio of
men to women on the whole 2:1 after the age of 65-70 years, the incidence of the

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same gender. The onset of ALS may occur from teenage years to the years 80 's,
however the peak age of onset occurs when 55-75 the year. The average age of
onset of sporadic ALS is 65 years old, the average age of onset familial ALS is 46
years old. 1

2.3. Etiology
There are three types of ALS: sporadic, familial, and a Guamian. The most
common form is sporadic. A small number of cases of inherited genetic disorder
(familial). 8
 ALS due to the abnormality genetic (familial) is caused by a genetic defect
in the antioxidant enzyme superoxide dismutase, which continuously
removes free radicals that are highly toxic, superoxide.
 The causes of ALS sporadic and Guamian is unknown. Several hypotheses
have been suggested including:
 The Toxicity Of Glutamate
 Oxidative Stress
 Mitochondrial dysfunction
 Autoimmune disease
 Infectious Diseases
 Exposure to toxic chemicals
 Heavy metals such as lead, mercury, aluminum, and manganese
 Deficiency of calcium and magnesium metabolism of
Carbohydrates
 A deficiency of growth factor

Classification classification of Motor Neuron Desease (MND): 9

a. Amyotrophic lateral sclerosis (ALS)
b. Progressive lateral sclerosis (PLS)
c. Progressive muscular's atrophy (PMA)
d. The involvement of the brain stem (Bulbar)

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 - Pseudobulbar palsy
- Progressive bulbar palsy

Table 1. The difference in symptoms in each type of MND

Type Macular UMN Macular LMN

ALS + +
PLS + _
PMA - +
Progressive bulbar
- +, in bulbar part
palsy
Pseudobulbar palsy +, in bulbar part -

Whereas in ALS itself, there are two types: 9

1. Familial
Familial ALS is characterized by the presence of family history and genetic
analysis of a gene or a defect that has been proven to be associated with the
disease. Familial ALS consist 5-10% of ALS total
2. Sporadic
90-95% rest of unknown cause so called as sporadic.

2.4. Pathophysiology 2
The exact molecular pathways causing the degeneration of motor neurons in
ALS is not known, but as with other neurodegenerative diseases, it is likely to be
a complex interaction between the various mechanisms of pathogenic provider
that may not mutually exclusive include:
1. Genetic Factors
Sporadic and familial ALS is clinically and pathologically similar, so there is
a possibility of having the same pathogenesis. Although only 2% of the patients
sufferers of ALS have mutations in SOD1, the discovery of this mutation is
important because it allows research on ALS research-based molecular

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pathogenesis in ALS. SOD1, is an enzyme which requires copper, catalyze
conversion radikals superoxide is toxic into hydrogen peroxide and oxygen. The
copper atoms mediated Catalysis process happens. SOD1 also has the capability
of prooksidasi, including the concentration of the hydroxyl radical formation, and
tyrosine nitration. Mutations in SOD1 are disturbing the antioxidant function
causes the accumulation of superoxide is toxic. Hypothesis function decline as the
cause of the disease was not proven to be due to excessive expression of SOD1
that termutasi (where the alanin mensubstitusi glycine at position 93 SOD1
(G93A) causes disease in spite of motor nerve SOD1 activity increased.
Therefore, SOD1 mutations cause the disease by disrupting the function of
toxicity, not because of a decrease in the activity of SOD1.

2. Excitotoxicity
This is a term for neuronal injury caused by excessive glutamate-induced
stimulation of postsynaptic glutamate receptor cell surface receptors such as
NMDA and AMPA receptors. This excess stimulation of glutamate receptor
thought to lead to an influx of calcium into neurons, which causes the formation
of nitric oxide is increased and thereby neuronal death. The level of glutamate in
CSF are increasing in some patients with ALS. This elevation has been associated
with loss of cell stimulation of amino acid transporter EAAT2 glial.
3. Oxidative Stress

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 Oxidative stress has been linked to some old neuro degenerative and note that
the accumulation of reactive oxygen species (ROS) causing cell death. Like
superoxide dismutase enzymes in the mutation of anti-oxidant 1 (SOD1) gene can
cause ALS, there is a significant interest in the mechanisms underlying
neurodegenerative process in ALS. This hypothesis is supported by the findings of
the biochemical changes that reflect the damage of free radicals and free radical
metabolism in the tissue sample is abnormal CSF and post mortem ALS patients.
4. Mitochondrial dysfunction
Morphological and biochemical mitochondrial abnormalities have been reported
in patients of ALS. The mitochondria of the patients ALS shows calcium levels
high and the decline in the activity of the respiratory chain complexes I and IV,
which involves the inability of energy metabolism.
5. Aksonal transport disorders
Motor neuron axons can reach up to one meter in length in humans, and rely
on an efficient intracellular transport system. This system consists of anterograde
transport system (slow and fast) and retrograde, and depends on the molecules '
motor ', a complex protein kinesin (anterograde) and dynein complex-dynactin
(retrograde). In patients with ALS, discovered mutations in the gene are known to
cause diseases of the kinesin motor nerves in the human neurodegenerative as
paraplegia spastik hereditary Type 2A disease and Charcot-Marie-Tooth.
Dynactin complex mutations causing the disorder of lower motor neuron with
paralysis of the vocal cords in humans.
6. Neurofilamen aggregation
Neurofilamen proteins together with Peripherin (an intermediate filament
protein) found in most motor neurons aksonal inclusion ALS patients. An isoform
of toxic peripherin (peripherin 61), has been found to be toxic to motor neurons
even when expressed on a simple level detected in korda spinalis patients ALS but
not control.
7. Protein aggregation
Intra-cytoplasmic Inclusions is the hallmark of sporadic and familial ALS.
However, it remains unclear whether pebentukkan the aggregate direct cause of

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cellular toxicity and has a key role in the pathogenesis of, if the aggregate may be
involved by the product of the process of neurodegenerasi, or if the aggregate
formation may be really be a beneficial process by being part of a defense
mechanism to reduce intracellular concentration of toxins protein.
8. Dysfunction inflammatory and non-neural cells contribution
Although ALS is not a primary or Autoimmunity disorder immune
disregulasi, there is sufficient evidence that the inflammatory process and non-
neural cells may play a role in the pathogenesis of ALS. The activation of
dendritic cells and mikroglial is the leading pathology ALS SOD1 transgenic mice
and humans. Non-nerve cells activated inflammatory cytokines such as interleukin
produces, COX-2, TNFa and MCP-1 upregulation, and evidence found in the CSF
or specimen of spinal cord patients ALS or in in vitro models.
9. The deficit in the neurotropik factors and signal line dysfunction
Decreased levels of neurotropik factors (e.g. CTNF, BDNF, GDNF and IGF-
1) have been observed in patients post-mortem and ALS in in vitro models. In
humans, three mutations in the gene VEGF found associated with an increased
risk of developing ALS sporadic, though this metaanalisis by the same author has
failed to show a relationship between haplotype VEGF and increases the risk of
ALS in man. The final process of neuron cell death in ALS allegedly similar to
cell death pathway hard-wired (apoptosis). Biochemical marker of apoptosis
detected in the patient's terminal stage ALS.

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2.5. Symptoms
ALS symptoms vary from one person to another but most have a complaint:
Table 2. The symptoms of ALS 11
UMN Dysfunction LMN Dysfunction Emotional symptoms

- Kontraktur - Muscle weakness - Laugh and cry

- Disartria - Fasikulasi. involunter
- Dysphagia - Atrophy. - Depression
- Dispneu - Muscle cramps
- Siallorhea - Hiporefleks
- Spastisitas. - Flasid
- Tendon reflexes are - Foot drop
quick or abnormal - Breathing
spread. difficulties.
- The presence of
pathological
reflexes.
- The loss of dexterity
with a normal force

Table 3. The relationship of complaints against motor neuron damage lokas 11

The medulla UMN Lesion Pseudobulbar spastisitas tongue
(other causes
including
stroke)

Disartria
Increased reflexes

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 labile emotions
Inkoordinasi
Function menelaan
and breathe

UMN lesion Disartria

and LMN Dysphagia
lesion jaw jerk reflex
increases

LMN Lesion Bulbar palsy Atrophy of

fasikulasi tongue
and Dysphagia

Kortikospinal UMN Lesion the spastic

Traktur weakness
increased reflexes
Stiffness
the extensor plantar
response

anterior kornu LMN Lesion The weakness of

the flasid
muscle fasikulasi
diaphragm muscle
weakness and
muscle
interkostalis

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 Progresifitas disease with increasing weakness and more muscles are
affected. When the weakness has spread to the torso, speech, swallowing and
breathing become compromised. Finally the ventilator support is required. Death
is usually a result of a complication of the paralysis is not active or the muscles
that control breathing. 5
ALS symptoms vary from one person to another in accordance with the
muscle groups that are affected by the disease. Tripped, dropped things, abnormal
fatigue in the arms and/or legs, raved talk, difficulties in talking loud,
uncontrollable laughing or crying, and muscle cramps and twitch all the
symptoms of ALS. ALS usually starts first at hand and will lead to problems in
dressing, bathing, or other simple tasks. This could develop into more on one side
of the body and generally runs to the hand or foot. If start on foot, walking would
be difficult. ALS can also start in the throat, causing difficulty in swallowing.
People who suffer from ALS does not lose their ability to see, hear, touch, smell,
or taste. the bladder and the muscles of the eyes are not affected, nor are sexual
drive and function. The disease does not affect one's mind. 8
Weaknesses can begin in the feet, hands, proximal arm, or oropharinx (to
speak Lisp or difficulty swallowing) disatria. Often the hands are affected first,
usually asymmetric. Gait was disrupted due to the characteristics of the muscles
are weak and footdrop, though proximal muscles sometimes are affected first. Or,
impaired gait spastik may occur. Slowly the weaknesses become more severe and
the various parts of the body start to be affected. Spasme muscles (the muscles
associated with hypersensitivity) and weight loss (resulting from a combination of
muscle that shrinks and dysphagia) is characteristic of the symptoms. Respiration
usually affected too late but, sometimes it may be the initial manifestation or even
the first. Respiratory muscle paresis was disrupted by interkostalis and the
diaphragm, or dysphagia can lead to pneumonitis and aspiration, which can occur
finally clinical Sensation is not affected, pain parestesia and allowed with this
diagnosis, unless there are complications, disease (such as diabetic neuropathy)
and the function of the bladder is spared. Pain is not a symptom of early but may
happen later when the limbs move. 6

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 The sign of the LMN must be clear to a valid diagnosis. Fasikulasi may
be seen on the tongue though without disartia. If there is a weakness and muscular
torso which tapers out fasikulasi usually have started look. tendon reflexes may be
increased or decreased. The combination of excessive reflex by Mark Hoffman on
the hand with a weak and muscle fasikulasi is actually a tnda which is
pathognomonic of ALS (except for the sidrom motor neuropathy). The sign
unequivocally umn abnormalities is babinsky and klonus. A spastic abnormalities
can be seen without an lmn on legs, weakness in the legs may not be found, but
inkoordinasi is proven with the awkwardness and clumsy in appearance as it
moves. 6
The motor cranial nerve nucleus involved in disartria, fasikulasi of the
tongue and the uvula distracted from movement. The weakness of the facial
muscles especially in the mentalis but this is usually not prominent. Disartria and
dysphagia caused by umn lesion (pseudobulbay palsy) is made clear by the
actions of the uvula are stronger on the innervation of the uvula on a whim, so can
not move well. But the strong response seen on faringeal or gag reflex. A common
manifestation of pseudobulbar palsy is emotionally labile with a reasonable or
laugh more often, menagis can be considered a misnomer as the depression
because the diagnosis, it is better considered a reflex phenomenon release
complex involved in emotional expression. The death caused due to respiratory
failure, aspiration pneumonitis, or emboli pulmo after a long immobilitas. 6

2.6. Diagnosis
A. The diagnosis of ALS requires the presence of:11
1. Signs of degeneration of the lower motor neurons (LMN) with an
examination of clinical, neuropathologic or electrophysiology.
2. Signs of degeneration of the upper motor neuron (UMN) with clinical
examination, and
3. Signs of progressive deployments in the region or to other areas, together
with the absence of

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 4. Evidence of another disease process electrophysiology might explain the
signs of LMN and/or degeneration of the UMN, and
5. Neuroimaging evidence of another disease process that may explain the
clinical signs and sign of electrophysiology

B. Clinical diagnostic categories are definitely on clinical criteria alone:11

1. Definitely ALS
UMN signs and LMN at least on three body parts
2. Most likely the ALS
UMN signs and LMN at least on 2 parts of the body, with a few marks on the
UMN rostral against mark LMN
3. Most likely ALS – Laboratory Supported the sign of UMN dysfunction
planning clinic. da LMN on only one part of the body. In addition, there is
a sign on the electromyography of active and chronic degeneration on at
least 2 extremities
4. The Possibility Of ALS
Clinical signs of UMN dysfunction and LMN are found simultaneously in one
piece, or a sign of UMN found on two or more parts of the body.

 UMN signs: Klonus, babinsky, no stomach skin reflex, hypertonia, lost

dexterity
 LMN signs: atrophy, weakness. If only fasciculation: search by EMG for
the active denervation
 Section: bulbar nerve, cervical, chest and lumbosakral

Can also use the other criteria of the World Federation of Neurology (WFN),
which must be: 13
 Evidence of UMN lesion
 Evidence of LMN lesion

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  Evidence of progresifitas
In using WFN criteria, there are 4 regio should know:
 Bulbar: Muscles of the face, mouth, throat.
 Cervical Muscle: back of the head, neck, shoulder, shoulder, upper
secondary.
 Thoracic: chest muscles and abdomen, and the central part of the spinal
muscles
 Lumbosacral: rear shoulder part Muscles, thighs, and lower secondary

Amyotrophic lateral sclerosis is difficult to diagnose since the beginning

because it may look similar to some other neurological diseases. Tests to rule out
other conditions might include. The surgeons after a careful neurological
examination, the presence of signs of UMN and LMN in anatomical segments of
the same with asymmetric localization were able to suspect a diagnosis of ALS.
The checks can be done among others: 12

1. Electrophysiology
Primarily to detect the presence of lesions LMN on the area involved. And to
get rid of other disease processes. It is very important to keep in mind that
physical examinations neurophysiologist who used to diagnose
neurophysiological disorders ALS suggestive alone is not enough to diagnose
without clinical support. 12
- Sensory and motor nerve conduction
Nerve conduction required to diagnose especially to define and exclude
other disorders of peripheral nerves, neuromuscular junction, and muscle
that can mimic or disrupt the diagnosis of ALS. 12
- Conventional electromyography 12
Concentric needle electromyography (EMG) provides evidence of
dysfunction LMN required to support a diagnosis of ALS, and must be
found in at least two of the four regions of the CNS: brain (cranial motor
neuron/bulbar), cervical, thoracic, or lumbosakral spinal cord (anterior

18
 Horn motor neuron). For the area of the brain stem that is enough to show
the changes in a single EMG muscle (such as the tongue, the muscles of
the face, jaw muscle). For the region of the spinal cord, chest it is enough
to show the changes in paraspinal muscle EMG either at or below the level
of T6 or on the abdominal muscles. For the cervical region and spinal cord
lumbosakral at least two muscles are innervated by different roots and
peripheral nerves should indicate changes in EMG. 12
El Escorial criteria revised requires that both evidence of denervation
active or ongoing and chronic partial denervation is required for the diagnosis of
ALS, although the relative proportions vary from muscle to muscle.
Signs of denervation active consists of:
1. the potential of fibrillation
2. positive sharp waves
Chronic denervation signs consist of:
a) Motor unit potential duration increased with an increase in the proportion
of polyphasic potentials, the amplitude is often increased.
b) Reduce the interference pattern with higher firing rate of 10 Hz (unless
there is a significant component of UMN, in terms of the rate of burning is
probably lower than 10 Hz).
c) Motor unit potentials is stable.
The potential of fasciculation is very important to find the characteristics
of ALS, although they can be seen in a normal muscle (fasikulasi benign)
and does not appear in all muscles of patients ALS. In fasikulasi benign
fasciculation of potential normal morphology, whereas on the potential
changes associated with fasciculation neurogenik there are abnormal and
complex morphology of sharply positive.
2. Transcranial magnetic stimulation and central motor conduction
Transkranial magnetic stimulation (TMS) allows non-invasive evaluation of
the motor pathways kortikospinalis, and allows the detection of UMN lesions in
patients who have no signs of the UMN. Motor cortical threshold, amplitude, time
and motor conduction period of silence can be easily evaluated by using this

19
method. Central motor conduction time (CMCT) is often a bit long for the
muscles of the extremities on patients at least one ALS. 12
3. Quantitative electromyography 12
Motor unit number estimation (Mune) is a technique of electrophysiology
specialist can provide quantitative estimates of the number of axons that innervate
the muscles or muscle groups. Mune is composed of a number of different
methods (incremental, dual stimulation, the point of a spike-triggered average, F-
wave, and statistical methods), with each has specific advantages and limitations.
Despite the lack of a single perfect method to perform the Mune, may have value
in the appraisal loss of motor axons progressively in ALS, and may have use as a
measure of end points in clinical trials.
4. Neuroimaging
MRI head/spine to get rid of the other structural lesions dandiagnosis in
patients suspected of ALS (tumor, spondylitis, siringomielia, the strokebilateral,
and MS) 12
5. Muscle biopsy and the neuropatologi
Primarily performed on patients with clinical presentation is not typical,
terutamadengan UMN lesion that is not clear. Biosi used to get rid of the
adanyamiopati, such as inclusion body myositis. 12
6. Other lab examination
There are a few other checks can be considered obligatory in the examination
of the patients of ALS. Clinical laboratory tests may be abnormal in the case
revealed a typical ALS include: 6
 Muscle enzyme (creatine kinase serum [unusual above ten times the upper
limit of normal], ALT, AST, LDH)
 Serum creatinin (associated with loss of skeletal muscle mass)
 Hypochloremia, bicarbonate increases (associated with the breathing
disorder continued).

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2.7. Complications
a. The respiratory system
Diaphragm and other respiratory muscles always affected, and most patients
die of respiratory koplikasi. This occurs primarily from the inability of the patient
to breathe due to respiratory muscle weakness. In patients with bulbar weakness,
aspiration of secretion or foods can occur and pneumonia, respiratory
management is, therefore, necessary to comprehensive care of patients with ALS.
Regularly measure the vital capacity in a sitting position and on his back. Most
often, the measurements lay downhill before measurement. Gravity assist in
14
lowering the diaphragm as the angle of inclination increases patient.
Respiratory weakness progresses, patients have increased difficulty with
movement of the diaphragm while on his back because of the Elimination of these
effects of gravity. This causes alveolar hipoventilasi and desaturation
oxyhemoglobin desaturation. Difficulty sleeping can be the first symptom of
hipoventilasi. The patient should be questioned about the habits of sleep regularly,
and if sleep disorders develop, measuring capacity it is important to sit and
terlentang. In addition, the oxygen saturation monitors overnight to assess the
hipoksemia night and the need for positive pressure ventilation night noninvasive
14
intermittent (IPPV).

2.8. The diagnosis of Motor Neuron Disease Other appeals 14

1. Primary lateral sclerosis (UMN)
 Progressive muscular's atrophy (LMN)
 Progressive bulbar palsy
2. Anatomic Abnormality/compression syndrome:
 Tumors of the medulla spinalis
Tumors of the medulla spinalis manifestas limb weakness can,
numbness, and signs of UMN lesion
 Sirinomyelia Syringomyelia is a disorder characterized by the
presence of development kavitas abnormal because of dilation of the
Canal central on korda spinalis. Kavitas is derived from the regio

21
 midservikal but can be stretched up to the medulla (produced
siringobulbia) or down to the regio torakal and lumbar. Kavitas
enlarged slowly for several years. The clinical syndrome characterized
mixed sensory and motor disorders among. Damage to the ventral
portion of the central gray lead to the sign of the LMN, weakness,
atrophy, fasikulasi of reflkes, loss of intrinsic hand arm always
happen. UMN signs on lower extremity occur with Cavity longer to
traktus kortikospinal. Siringobulbia can lead to the complete vocal
cords, diastria, nistagmus, weakness of the tongue and horner's
syndrome.
 Cervical spondylosis
Can be found the combination of UMN lesion and LMN on the
superior extremity muscles. Usually accompanied by sensory
disorders. Although cervical myelopathy spondilosis heavy can
sometimes cause confusion with MND, especially if there is
spastisitas and hyperrefexia in the lower limb in conjunction with
muscle atrophy and fasikulasi on the upper limbs, not fasikulasi may
cause weakness and Weakness15. Members of a progressive motion,
asymmetric, combined signs of UMN and LMN on your arms,
paraparesis spastik, sometimes fasikulasi in arm.12
3. Infection
 Lyme disease
Infection neurological manifestation of Lyme disease include
meningitis and polyradiculoneuropathy. The second and third stage
Lyme disease related to neurological changes that can cause
neuropathy, motor aksonal low. Lyme disease is caused by bacteria of
the spirochete (Borrelia burgdorfere). Teratology studies on Nerve
roots occurred in early or late stages of the disease. The symptoms can
be weakness, sensory disturbance and hiporefleks on the affected nerve
roots.
 Myelopati

22
 HIV Myelopati related to HIV infection are usually seen at the stadium
later than the illness. It is dikaakteristikkan with the ganggua walking
(gait) with sensory disorders, sphincter and the reflex ganggua fast. On
the mielopati of HIV also are a sign of UMN and LMN. Peripheral
neuropathy (damage to axons) is a sign of HIV Clinic. 8
4. NM Junction 16
 Myasthenia gravis
It is an autoimmune disease of the neuromuscular transmission and
disruptive at the neuromuscular junction due to deficiencies/damage
receptors Ach. The typical complaints of muscle weakness after a
momentary/used and improved after the break. Symptoms of initiation
(fokal bulbar muscles, limb, muscle, muscles of the eye (monocular,
ptosis. Miastenia gravis can also cause weakness in the muscles of
breathing. There was no sign of weakness and fasikulasi UMN.
5. Endocrine: 16
 Hipertiroid Manfetasi of Neurology of hyperthyroidism bervaariasi
including perubaha mental status, seizures, motion abnormality such as
tremor and korea, eye disorders, weak, atrophy, fasikulasi. in addition,
patients with hyperthyroidism in General has reflex tendons in a fast,
da some patients had damage from traktus kortikospinal and the sign
of babinski. Patients with hyperthyroidism may develop combines with
klemahan and UMN signs resembling ALS. Of course most patients
with hyperthyroidism have evidence of toxic goiter, ansietas, and
insomnia that bias is distinguished with ALS. It is important to be
revealed, however, in patients with hipertiroidismedapat manifests
with apathy and depression called apathetic hyperthyroidism.
 Hyperparathyroidism
Neurological Manifestations of hyperparathyroidism patients with
hiperparatiroid generally associated with hiperkalsemia,
hipofosfatemia, and increased parathyroid hormone levels of consists
of mental status changes such as lethargi, confused, and ultimately

23
 hiperkalemia. when a comma is not severe or acute but weakness and
fatigue may appear as symptoms in primary hiperparatiroid. Rare
symptoms patients evolved from myopathy. Rare hiperparatiroid and
ALS occurs simultaneously on the patient, the possibility increases if
the increased levels of parathyroid hormone contributes to the
progression of motor neuron syndrome. Hiperkalsemia and increased
parathyroid hormone levels but can help distinguish between these
endocrine diseases with ALS.

Table og Diffren diagnostic.

2.9. Management
A. Pharmacology
1. Therapy causative 17
 Glutamate antagonists: Riluzole, gabapentin, Lamotrigine,
dextrometrophan, chain amino acid

24
  Antioxidant Vitamin E, Asetilsistein, Selegiline, Creatine, Coenzyme
Q10, Selenium
 Neutrotropik factor
Have factor neutrotropik, insulin-like growth factor
 Imunomodulator
Gangliosides, interfero, plasmaaresis, intravenous immunoglobulin
 Anti viral
Amantadine, tilorone

2. Symptomatic Therapy
Symptomatic Dugs
Numb fingers Karbamazepin, phenitoin

Spastisitas Haloperidol, tizanidine,

dantrolen
Atropine, Hyoscine
Increased secretion of saliva hydrobromide, Hyoscine
butylbromide
Glycopyrronium, Hyoscine,
scopoderm, Amitriptyline
Persistent secretion of saliva Carbocisteine, Propranolol,
and bronchial Metoprolol
Laryngospasm Lorazepam
Pain Analgesic Opioids, Non-
steroidal
Labile emotions Tricyclic antidepressant,
Selective serotonin-reuptake
inhibitors, of L-dopa,
Dextrometorphan and
quinidine

25
 Depression Amitriptyline, Citalopram
Insomnia Amitriptyline, Zolpidem
Anxietas Lorazepam

B. Non Pharmakology 8
1. Physical therapy
One side effect of this disease is spasme or uncontrolled muscle contractions.
Physical therapy cannot restore normal muscle function, but it can help in
preventing painful muscle contractions and muscle strength in maintaining normal
function. Physical therapy should involve family members, so they can help keep
this terpai for patients ALS.
2. Talk therapy
Speech therapy may also help in maintaining a person's ability to speak.
Swallowing therapy is also important, to assist swallowing while eating and
drinking. This treatment helps to prevent choking. It is recommended to position
the patient's head and the position of the tongue. Patients with ALS also have to
change the consistency of the food to aid swallowing.
3. Occupational therapy
So that the patient can perform daily activities/work more easily without the help
of others.
4. Respiratory therapy
When the ability to breathe, a respiratory therapist needed to measure breathing
capacity. This test should be done on a regular basis. To make breathing easier,
the patient should not lie down after eating. Patients should not eat too much,
because they
can increase the pressure of the stomach and prevents the development of the
diaphragm. When sleeping, the head must be elevated 15 to 30 degrees so that the
abdominal organs away from the diaphragm. When respiratory capacity falls
below 70%, noninvasive respiratory assistance must be provided. This involves a
mask connected to a mechanical ventilator. When the capacity of the breathe of
fallen below 50%, the permanent hook-up to the ventilator must be considered.

26
2.10. The prognosis
ALS is a fatal disease. The average life is 3 years from clinical onset of
weakness. However, a longer survival is not rare. About 15% of patients with
ALS live five years after diagnosis, and about 5% survive for more than 10 years.
Long-term survival is associated with younger age at the moment of onset, men,
and members of the body than the bulbar onset of symptoms. Rare reports of
spontaneous remission exists. 1
Motorneuron disease that limited such as PMA, PBP, PLS who did not develop
into a classic ALS progresifitas has a slower and longer hidu continuity. 1

27
 CHAPTER III
CONCLUSION

3.1. Conclusion
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that
causes severe muscle weakness, disability, and eventually die due to the
degeneration of motor neurons in the primary motor cortex, brain stem and
Medulla spinalis. The cause of ALS is unknown, although 5-10% of cases are
familial.
In this disease the arrangement of somatosensory altogether is not
interrupted. Thus, its manifestation consists of pure movement disorders, who
showed signs of UMN paralysis and LMN are berbauran. In the meantime,
hiperefleksia, klonus and pathological reflex can be found side by side with
muscle atrophy and arefleksia on a single sufferer.
Management of ALS is a form of support (support) against patients, palliative,
and multidisciplinary. Non-invasive ventilation may extend survival and improve
quality of life. Riluzole is the only drug that has been shown to extend survival.
Figure haraan average life is 3 years from clinical onset of weakness. However, a
longer survival is not uncommon. About 15% of patients with ALS live five years
after diagnosis, and about 5% survive for more than 10 years.

28
 REFERENCES

1. Carmel Armon. 2011. Amyotrophic Lateral Sclerosis (ALS) in Physical

Medicine and Rehabilitation Available at http://
http://emedicine.medscape.com/article/1170097-overview. [cited : August
26 2011]
2. Lokesh C Wijesekera, P Nigel. Leigh.2009. Amyotrophic lateral sclerosis
www.ojrd.com/content/pdf/1750-1172-4-3.pdf. [cited : August 26 201]
3. Lokesh C Wijesekera, P Nigel. Leigh .2011. Amyotrophic lateral sclerosis
www.ojrd.com/content/4/1/3 [cited : August 26 201]
4. Mahar mardjono, Priguna S. Neurologi klinis dasar. Jakarta: Penerbit
Dian rakyat. 2006
5. Thomas Farley, MA.2004. Amyotrophic lateral sclerosis.
www.spinalcord.ar.gov/resource/ ALS.pdf. [cited : August 26 201]
6. V. Silani et al.2011. The diagnosis of Amyotrophic Lateral Sclerosis.
www.neuro.it/documents/.../Silani_3.pdf. [cited : August 26 201]
7. Anonym. 2005. Amyotrophic lateral sclerosis.
www.researchals.org/uploaded_files/mdph_alsreport_211aDS.pdf. [cited :
August 26 201]
8. Ronald Sterit . 2006. Amyotrophic lateral sclerosis.
www.naturdoctor.com/Chapters/.../ALS.pdf. [cited : August 26 201]
9. Devi Uma. 2007. Motor neuron disease.
api.ning.com/.../motorneurondisease. pdf. [cited : August 26 201]
10. Ammar Al-Chalabi, 1999. Genetic risk factors in amyotrophic lateral
sclerosis www.ammar.co.uk/phdam.pdf [cited : August 26 201]
11. Anonym. 2007. A Guide To Alspatient Care For Primary Care Physicians
www.als.ca/.../guide/AGuidetoALSPatientCare [cited : August 26 201]
12. Lokesh C Wijesekera, P Nigel. Leigh .2009. Amyotrophic lateral sclerosis
www.ojrd.com/content/pdf/1750-1172-4-3.pdf[cited : August 26 201]

29
13. Jinsy A Andrews.2011. Amyotrophic lateral sclerosis
http://www.medlink.com/medlinkcontent.asp [cited : August 26 201]
14. Noah Lechtzin . 2006.Respiratory Effects of Amyotrophic Lateral Sclerosis
Problems and Solutions
www.rcjournal.com/contents/.../08.06.0871.p [cited : August 26 201]
15. Sathasivam S. 2010. Motor neurone disease: clinical features, diagnosis,
diagnostic pitfalls and prognostic markers.
smj.sma.org.sg/5105/5105ra1.pdf. [cited : August 26 201]
16. Jacqueline Cristini.2006. Misdiagnosis and missed diagnoses in patients
with ALS. mmedia.haymarketmedia.com/.../als0706_1803... [cited : August
26 201]
17. Lewis P. Rowland, M.D., and Neil A. Shneider.2001. Amyotrophic
Lateral Sclerosis. www.nejm.org/doi/.../NEJM20010531344220 [cited :
August 26 201]
18. Acary Souza Bulle Oliveira , Roberto Dias Batista Pereira. 2009.
Amyotrophic lateral sclerosis (ALS).
http://www.scielo.br/scielo.php?pid=S0004282X2009000600015&script=
sci_arttext.pdf. [cited : August 26 201]

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