1

Do you
remember this
Place your screenshot here
social media
challenge?
A successful campaign
which raised over $220M
worldwide for ALS
research
AMYOTROPHIC
LATERAL
SCLEROSIS
(ALS)
 4

WHAT IS ALS?
× AKA Motor Neuron Disease (MND)
× AKA Lou Gehrig's disease
× Neurological disease that attacks
the nerve cells (neurons)
responsible for controlling
voluntary muscles
 5

WHAT IS ALS?
× ALS is a degeneration of somatic
motor neurons extending from
upper motor cortical pyramidal
neurons to lower motor neurons
of the brainstem and cord
 6

1.
Background
Brief Review and
Types of ALS
 7

Brief Review and Types of ALS

Background Information
× ALS is the most common degenerative disease of the motor
neuron system
× Name: a-myo-trophic = no-muscle-nourishment.
Amyotrophy referring to the atrophy of muscle fibers,
which are denervated as their corresponding anterior
horn cells degenerate.
lateral sclerosis = changes in the lateral corticospinal
tracts of the spinal cord as upper motor neuron
(UMN) axons in these areas degenerate and
replaced by fibrous astrocytes (gliosis)
 8

Brief Review and Types of ALS

Background Information
× First described by Jean-Martin
Charcot (French neurologist)
× ALS is AKA Charcot disease
× Best recognized in the United States
after the baseball player Lou
Gehrig’s diagnosis with the disease
 9

Brief Review and Types of ALS

Background Information
× First described by Jean-Martin
Charcot (French neurologist)
× ALS is AKA Charcot disease
× Best recognized in the United States
after the baseball player Lou
Gehrig’s diagnosis with the disease
 10

Main ALS Presentations

× Spinal-onset Amyotrophic Lateral
Sclerosis (70%) – muscle weakness
and atrophy in the limbs and trunk
× Bulbar-onset Amyotrophic Lateral
Sclerosis (50%) - cognitive and
language impairments
× sALS that exhibit bulbar changes
with disease progression – 85%
patients
 11

Variants of ALS
CLASSIC ALS
× Reserved for the form of disease
that involves upper and lower motor
neurons
× Primary lateral sclerosis: pure UMN
involvement
× Progressive muscular atrophy: pure
LMN involvement
 12

Variants of ALS
PROGRESSIVE BULBAR PALSY
× restricted to bulbar muscles
× to patients with initial involvement
of bulbar muscles, the disease
evolves to classic ALS.
 13

Variants of ALS
SPORADIC ALS
× 90% cases of ALS
× sporadic - cause of disease are
unknown
× mean age of onset of sporadic ALS
is 65 years
 14

Variants of ALS
FAMILIAL ALS
× family history of ALS
× 5% familial ALS cases worldwide
× mean age of onset of familial ALS
ranges from 46-55 years
× inherited in an autosomal dominant
pattern / X-linked or autosomal
recessive inheritance
 15

2.
Epidemiology
Incidence, Distribution,
and Control of Diseases
 16

Incidence per Country

our office
 17

Incidence per Country

× EUROPE: 2.1 to 3.8 cases per
100,000 people
× SWEDEN: 3.8 cases per 100,000
people
× SCOTLAND: 3.8 cases per 100,000
people
× NORWAY: 2.1 cases per 100,000
people
 18

Incidence per Country and Worldwide

× KOREA: 1.2 cases per 100,000 people
× CHINA: 1.2 cases per 100,000 people
× UNITED STATES: 3.7 cases per
100,000 people
× WORLDWIDE: ALS prevalence is 5-7
people per 100,000 worldwide
 19

Prevalence per Race

× National ALS Registry: European-
American ALS patient was found to
be more than doubled the
prevalence of African-American ALS
patients (5.4 vs. 2.3 per 100,000)
× US: ALS affects whites more often
than nonwhites; the white-to-
nonwhite ratio is 1.6:1
 20

Prevalence based on Sex

× Male sex has a higher risk of having ALS but
may differ between countries.
× Worldwide: incidence of ALS is higher in men
than in women, with an overall male-to-
female ratio of 1.5-2:1.
× US: Male to female ratio is 3:2
 21

Prevalence based on Age

× Mean or median age of ALS onset: between
51 and 66 years
× The ALS Association (2020): ALS usually
affects people between ages of 40 and 70
 22

Prevalence based on Age

2013: Ages 70-79 is the highest prevalence rate of ALS once again, at
20.5 cases per 100,000. Adults from ages 18-39 once again have the
lowest prevalence rate, which is below 2 cases per 100,000.
 23

3.
Etiology
ALS’s Cause and Manner
of Causation
 24

Cause of ALS
× National Institute of Neurological Disorders
and Stroke (2013): the cause of ALS is
unknown, and scientists have not yet
discovered why ALS strikes some people and
not others
× Studies suggest that genetics and
environment play a role in
developing ALS
 25

Genetic Factors Affecting ALS

Development
× Mendelian autosomal dominant pattern of
inheritance
× Only requires one parent to carry the gene
responsible for the disease
 26

Gene Mutations in Familial ALS

SOD-1Mutations (superoxide dismutase 1)
× Numerous hypotheses have been proposed to
explain SOD1-mediated toxicity such as
misfolding proteins
 27

Gene Mutations in Familial ALS

TARDBP Gene Mutations (Thrombocytope
nia-absent radius DNA-binding protein 43)
× Codes the TDP-43, have been found in 5% of
patients with familial ALS
 28

Gene Mutations in Familial ALS

C9orf72 Mutation
× Patients have an earlier bulbar onset of
disease, cognitive and behavioral impairment,
and a family history of frontotemporal
dementia
 29

Environmental Risk Factors

SMOKING
× studies have shown that active smokers have
approximately double the risk of developing
ALS compared with never smokers
 30

Environmental Risk Factors

MILITARY SERVICE
× close scrutiny has cast doubt on the quality
of the evidence supporting the role of these
factors in triggering ALS
 31

Environmental Risk Factors

SPORTS
× subsequent reports suggested that a form of
motor neuron disease might develop in
individuals, such as boxers, who have
sustained repetitive injuries to the brain
 32

4.
Pathology
Course, Risk Factors, and
Transmission
 33

ALS Pathology
1. Precentral gyrus atrophy
2. Corticospinal tracts with variable patterns
of degeneration
3. Loss of cortical pyramidal motor neurons
and gliosis
 34

Course of the ALS Disease

1. Early in the disease: surviving nerve fibers
establish connections and reinnervate motor
units that have lost their connection to
axons that have died
2. Larger motor units are formed. Later in the
disease, when the motor neurons that
supply the large motor units die,
group atrophy ensues.
 35

ALS Mode of Transmission

× Only known mode of transmission:
familial and sporadic ALS, which stems
from genetics
× People who have Sporadic ALS has a
possibility of carrying ALS-causing genetic
mutations that can be passed on to their
offspring.
 36

ALS Risk Factors

1. HEREDITY AND GENETICS: 5 to 10% cases
inherit ALS from familial ALS . 90% of ALS
cases occur without family history.
2. AGE: risk of having ALS increases with age,
with ages 50 to mid60s being the most
common when being diagnosed
3. GENDER: more men have slightly
developed ALS more than women
 37

5.
Pathophysiology
Associative-Disorders
Related to ALS Disease
 38

Pathophysiology
× ALS is a clinical diagnosis for
different pathophysiologic cascades
that share the common consequence
of causing preferential progressive
loss of motor neurons and the
orderly dismantling of the motor
neuron system
 39

ALS Mechanisms
AXONAL DEGENERATION
× motor axons die by Wallerian
degeneration in ALS, and large
motor neurons are affected
× result of the death of the anterior
horn cell body, leading to
degeneration of the associated
motor axon
 40

ALS Mechanisms
CELL DEATH DUE TO PATHWAYS
Pathways that lead to cell death in
ALS may be mediated by the following:
× a. Oxidative damage
× b. Mitochondrial dysfunction
× c. Caspase-mediated cell death
(apoptosis)
 41

ALS Mechanisms
CELL DEATH DUE TO PATHWAYS
× d. Defects in axonal transport
× e. Abnormal growth factor
expression
× f. Glial cell pathology
× g. Glutamate excitotoxicity
× h. Aggregation of abnormal
proteins
 42

ALS Mechanisms
PROGRESSIVE BULBAR PALSY
× variant form of amyotrophic lateral
sclerosis (ALS)
 43

6.
Clinical
Manifestaitons
Complications and Signs
& Symptoms
 44

Clinical Maifestations
× 75-80% of patients: symptoms begin with
lower limb involvement:
× Tripping, stumbling, or awkwardness
when running
× Foot drop; patients may report a
"slapping" gait
 45

Clinical Maifestations
× Initial complaints with upper limb onset
include the following:
× Reduced finger dexterity, cramping,
stiffness, and weakness or wasting of
intrinsic hand muscles
× Wrist drop interfering with work
performance
 46

Clinical Maifestations
× 20-25% of patients: bulbar onset initial
complaints are as follows:
× Slurred speech, hoarseness, or decreased
volume of speech
× Aspiration or choking during a meal
 47

Clinical Maifestations
× Complain of weakness
× Atrophy
× Fasciculations
× Muscle cramping
× Focal and asymmetrical onset of weakness
 48

Clinical Maifestations
× Patients present initially with
spasticity dysarthia or facies, or
both with no detectable lower
motor neuron signs.
× Individuals with classic ALS
show signs of:
× Dementia (3.5%)
× Parkinsons (1.5%)
 49

Complications
× Progressive inability to perform activities of
daily living (ADLs), including handling
utensils for self feeding
× Deterioration of ambulation
× Aspiration pneumonia
× Respiratory insufficiency
 50

Complications
× Complications from being wheelchair-bound
or bedridden, including decubitus ulcers and
skin infections
× Deep vein thromboses and pulmonary
emboli
 51

7.
Differential
Diagnosis
ALS’s Difference to Other
Conditions
 52

Diagnosis
× Definitive diagnosis may not be
possible with early ALS
× Confirmation of the disease may
require a period of observation to
document its progressive nature and
to exclude alternative diagnoses
 53

Diagnosis
× 8% of patients initially diagnosed
with ALS eventually finds out
alternative diagnosis because of
atypical presentation and lack of
progression
× 50% of them have potentially
treatable diseases
 54

Diagnosis
× Most common alternative diagnoses of ALS
are multifocal motor neuropathy and
Kennedy’s syndrome
× 50% of them have potentially treatable
diseases
 55

Multifocal Motor Neuropathy

× Progressive, assymentric weakness; occurs in
distribution of peripheral nerves
(distinguishing factor from ALS)
Kennedy’s syndrome
× commonly confused with
bulbar-onset ALS
 56

Multifocal Motor Neuropathy

× Progressive, assymentric weakness; occurs in
distribution of peripheral nerves
(distinguishing factor from ALS)
 57

Differential Diagnosis
× A comprehensive diagnostic workup
for ALS include:
• Electrodiagnostic tests including
electromyography (EMG) and nerve
conduction velocity (NCV)
• Blood and urine studies
• Spinal Tap
• MRI
 58

Differential Diagnosis
• Myelogram of the spine
• Muscle and/or nerve biopsy
• Neurological Examination
 59

Differential Diagnosis
Other disease and disorders that mimic
ALS include disorders of motor neuron:
× Spinal muscular atrophy
× X-linked spinobulbar muscle
atrophy
× Poliomyelitis or post-polio
syndrome
× Hexosaminidase A deficiency
 60

Differential Diagnosis
Other disease and disorders that mimic
ALS include disorder of motor nerves:
× Multifocal motor neuropathy
× Chronic inflammatory demyelinating
neuropathy
× Cramp-fasciculation syndrome
× Heavy metal poisoning
 61

Differential Diagnosis
Other disease and disorders that mimic
ALS include disorder of the
neuromuscular junction:
× Myasthenia gravis
× Lambert-Eaton myasthenic
syndrome
 62

Differential Diagnosis
Other disease and disorders that mimic
ALS:
× Structural CNS and spinal lesions
× Myopathy
× Thyrotoxicosis
× Hyperthyroidism
× Subacute combined degeneration
× Coeliac disease
 63

8.
Medical
Treatment
Management and
Symptomatic Treatment
 64

Medical Intervention
for ALS
Proper care by
multidisciplinary team,
communication of
diagnosis and disease-
modifying therapies and
symptomatic treatment
 65

Medical Intervention
for ALS
Prolongation of life and
maintaining quality of life
include taking proper
care of patient’s diet and
nutrition.
 66

Disease Modifying
Therapy for ALS

RILUZOLE
× the only effective
neuroprotective therapy for
ALS that prolongs patient
survival by at least 3-6
months
 67

Symptomatic Treatment for ALS aims to

improve QoL of patients and caregivers
× Sialorrhea –amitriptyline, atropine drops and
scopolamine patch
× Bronchial secretions –mucolytic agent, beta-
blockers, and humidifiers
× Cramps – prevented with exercise, physical
therapy, massage, and hydrotherapy
 68

Symptomatic Treatment for ALS aims to

improve QoL of patients and caregivers
× Spasticity – treated with baclofen and
tizanidine (pharmacologic), and physical
therapy (non-pharmacologic)
× Depression and Anxiety – antidepressants
 69

Respiratory Management for ALS

× Monitoring respiratory function
× Noninvasive positive-pressure ventilation
× Preferred therapy for respiratory
insufficiency
× Increases survival by several months
 70

Respiratory Management for ALS

× Mechanical ventilation
× Prevents aspiration and prolongs survival
× Labor intensive (requires 24 hour care)