Amyotrophic Lateral Sclerosis (ALS)

Aka: Lou Gehrig’s Disease

Definition
 A rapidly progressive neurodegenerative disease that affects nerve cells of brain and spinal
cord characterized by weakness, spasticity, and muscular atrophy with respiratory
compromise leading to death.
Anatomy and Physiology

ALS is a disease of both upper and lower motor neurons. All motor neurons are upper motor neurons so long as they are encased in
the brain or spinal cord. Once the neuron exits the spinal cord, it operates as a lower motor neuron.

Upper Motor Neurons

The upper motor neurons are derived from corticospinal and corticobulbar fibers that originate in the brain’s primary motor cortex.
They are responsible for carrying impulses for voluntary motor activity from the cerebral cortex to the lower motor neurons.

Axons from these two tracts (collectively referred to as the pyramidal tracts) begin at the motor cortex of the brain but travel different
paths in the central nervous system:

 The corticospinal tract projects to control extremity muscle activity

 The corticobulbar tract projects to cranial nerves

The corticospinal tract fibers traverse through the brainstem where most of them cross at the medulla becoming the lateral pyramidal
tract. Their course then continues on down the spinal cord where they travel in the anterior horn before exiting the spinal cord to control
extremity muscle activity. Unlike the corticospinal tract, the corticobulbar fibers do not project down the spinal cord. Inst ead they
provide supply to the cranial nerve nuclei. Most specifically, the corticobulbar fibers affect the following cranial nerves and functions:
 V (Trigeminal – facial, mouth and some tongue sensation)  VII (Facial – facial expression)  IX (Glossopharyngeal – salivary
controls)  X (Vagus – laryngeal supply)  XII (Hypoglossal – tongue innervation)

In some instances, the motor neuron pathways can also affect the brain’s limbic system which has impact on mood, expression and
memory. This especially occurs in ALS patients who have a more bulbar or corticobulbar involvement with their disease.

Lower Motor Neurons

Once a nerve exits the spinal cord it is no longer an upper motor neuron, it becomes a lower motorneuron providing direct supply to
peripheral structures.
Pathophysiology
Glutamate ALS is characterized by a progressive
degeneration and loss of motor neurons in the
Calcium Influx spinal cord, brainstem, and motor cortex. As
Degradation of Neurons motor neurons degenerate, they can no longer
control the muscle fibers they innervate. So if an
Death of Neurons neuron madamage asya di na nakakasend signal
pakadto aton muscles causing weakness,
Denervation/Damaged of Motor Neurons difficulty breathing and even difficulty walking
na maresult han ALS.
No Action Potential Transmitted
ALS

Epidemiology
 Age onset: Mid to Late ’50s
 M>F
 70-80% Limb Onset
 20-30% Bulbar Onset
Etiology
 Unknown
o Risk Factors:
 Gender
o Men are exposed to higher levels of testosterone before birth, and they
are also more likely than women to develop ALS. More recently, studies
have shown that in both men and women, testosterone is also essential
for healthy neurons: it protects them from damage after injury or
disease.
 Age
o Although the disease can strike at any age, symptoms most commonly
develop between the ages of 55 and 75.
 Family Hx
o About 5–10% of ALS patients have a family history of the disorder. A
mutation in the SOD1 gene on chromosome 21 has been identified as a
cause of this type of ALS.
Notes
Multiple Mechanism:
 Oxidative Stress
 Exogenous Neurotoxicity
 Excitotoxicity
 Impaired Axonal Transportation
 Protein Aggregation
 Apoptosis
 Lifestyle
Clinical Manifestation
 Dysphagia
 Dysarthria Notes
 Pain Progression
 Dyspnea
 Spasticity  Lose the ability to walk or use hands and arms
 Fasciculation  Lose the ability to speak and swallow
 Muscle Weakness Late Stage
 Dementia
 Muscle atrophy  Respiratory Failure
 ↓ ROM  Aspiration Pneumonia
 Oculomotor nerve of extraocular muscle is affected may
 Impaired Gait resemble locked in syndrome
 Difficulty in ADL’s

Differential Diagnosis

ALS MG
Neurodegenerative Disease Autoimmune Disease
M>F F>M
Difficulty in clearing the Throat Regurgitation through the nose due to
palatal weakness
MC cause of death: Respiratory Failure
MC cause of death: Cardiovascular Disease

Bulbar Symptoms
Head Drop
Facial Weakness
Muscle Weakness
Fatigue
PT Assessment
 Pt Hx
 OI
 Pain
 Cognition
 CN Integrity
 Sensory
 ROM
 MMT
 Balance
 Posture
 Gait
 FIM
 Respiratory Examination
 Pulse Oximeter
 Capillary Refill
 Respiratory Excursion
 Fremitus Test
 Egophony
 Bronchophony
 Whispered Pectoriloquy

Medical/Surgery Management
 No Definitive Diagnostic Test: EMG
 Diazepam: Seizure and Spasm
 Baclofen: Spasticity
 Analgesics: Pain
 Riluzole: Glutamate Inhibitor
 Mucolytics: Reduce viscosity of mucus
 Surgery: Tracheostomy
PT Management
 Pt Education – Prevent further complications
 PROM, AROM, AAROM Exercise - ↑ Jt mobility
 Breathing Exercise – To help ease breathing difficulties
 Endurance Exercise – To improve functional capacity
 Stretching Exercise – To reduce spasticity
 Strengthening Exercise – Prevent muscle weakness and atrophy
 Low Impact Aerobic Exercise
 PNF Exercise
NOTES
Subtypes of ALS
Familial ALS
 Associated with copper-zinc superoxide dismutase 1 (SOD1)
Juvenile ALS
 Onset: Before 25 y/o
Types:
 ALS 5
o Most Common; Autosomal Recessive
o Mutation of chromosome 15q
 ALS 2
o Autosomal Recessive
o Mutation of chromosome 2q33
 ALS 4
o Autosomal dominant
o Mutation of chromosome 9q34
Western Pacific ALS
 Parkinsonism Dementia Complex (Guamanian)
 Combination of ALS, parkinsonism, and dementia (ALS-PD complex) found in high
incidence in some small populations in the western pacific (i.e. Guam)
 Hypothesis: Lack of calcium in soil and water leading to secondary hyperthyroidism and
subsequently, neuronal damage
 Also can be due to a cycad seed (found only in the western pacific region used as food and
medicine)
Groot Eylandt Motor Neuron Disease
 Rare disorder affecting Australian aborigines
Post-encephalitic (Encephalitis Lethargica) ALS
 Peaked in 1920 and 1924 during an outbreak of encephalitis, those who survived developed
ALS 10-30 years later
Variants of ALS
Progressive Bulbar Palsy
 When motor cells of the medulla oblongata are
involved.
Progressive Muscular Atrophy
 Muscles of the trunk and extremities are affected first
as a result of degeneration of the motor neurons in
the spinal cord.
Classic ALS
 Atrophy of the bulbar and trunk muscles, accompanied by signs of corticospinal tract
involvement.
 Motor neuron disease resulting from degeneration of motor nerves throughout the nervous
system, which involves UMN as well as the LMN.
 Most common of all motor neuron diseases which involves a selective neuronal
degenerative loss in the frontal cortex, motor cranial nerve nuclei (except CN III) and
Anterior Horn Cells in the ventral gray matter of the spinal cord.
Clinical Picture
 LMN (Lower Motor Neurons)
o Atrophy (most apparent in the hand; cat be unilateral or bilateral)
o Weakness
o Fasciculation
o Paralysis
 UMN (Upper Motor Neurons)
o Spasticity and Increased
o Muscle Pain
o Clonus
Triads of ALS
 General Hyperreflexia
 Atrophic Weakness of Hands and Forearm
 Spasticity of Legs
Lifespan
85% = 3 years
10% = 5 years
5% = 10 years
Possible Question
1. What cranial nerves are involved?
o CN 5, 7, 9, 10, and 12
2. Spared?
o Mental Status
o Ocular Muscles
o Onufrowicz Nucleus (Onuf’s nucleus)
o Non-motor CN
o Cerebellum
o Sensory System
3. Poor Prognosis?
o Bulbar Dysfunction
o Pulmo Dysfunction
o Old Age
o LMN sign of the onset
o Short time period from onset to diagnosis
4. Accepted criteria considered as standard for the diagnosis of ALS for clinical practice,
therapeutic trials, and other research purposes?
o El Escorial criteria in 1994
5. What examination procedures are used to help The diagnosis of ALS requires the presence of (1)
support the diagnosis of ALS? LMN signs by clinical, electrophysiological, or
o With the exception of one genetic test, no neuropathological examination; (2) UMN signs by
clinical examination; and (3) progression of the
definitive diagnostic test or diagnostic biological disease within a region or to other regions by clinical
marker exists for ALS. For individuals with a examination or via the medical history. The absence
clinical presentation of ALS, laboratory studies, of (1) electrophysiological and pathological evidence
of other diseases that may explain the UMN and LMN
EMG, nerve conduction velocity studies, muscle signs; and (2) neuroimaging evidence of other disease
and nerve biopsies, and neuroimaging studies are processes that may explain the observed clinical and
used to support the diagnosis of ALS and to electrophysiological signs are also evaluated.
exclude other diagnoses.
6. Identify and define the major classifications of ALS included in the El Escorial criteria
developed by the World Federation of Neurology Research Group on Motor Neuron
Diseases
o Clinically Definite
o Clinically Probable
o Clinically Probable with Laboratory Support
o Clinically Possible
7. What are the chief goals of exercise in ALS?
o Maintenance of range of motion of all joints
o Prevention of painful contractures
o Maintenance of tone and strength of muscles not yet or minimally affected by the
disease
o Maintenance or improvement of cardiovascular health, mood, and energy level (this
can be accomplished with low-impact exercise)
8. Why is ALS also referred to as Lou Gehrig’s disease?
o ALS first came to the wide public attention when the Hall of Fame career of Yankee’s
first baseman, Lou Gehrig, was cut short by the disease in 1939. Gehrig died in 1941.
Many people still use the term, Lou Gehrig’s disease, when referring to ALS.
9. How is the Ice Bucket Challenge related to ALS?
o The Ice Bucket Challenge is a campaign to promote awareness of amyotrophic lateral
sclerosis (ALS) and encourage donations for research. A person is filmed as a bucket
of water and ice is dumped over the individual's head.