Amyotrophic Lateral Sclerosis

Brief Anatomy

UPPER MOTOR NEURON

● Originate in the cerebral cortex and
travel down to the brainstem or spinal
cord
● Generally concentrated in the motor
region of the brainstem or cerebral
cortex
● Utilize glutamate to relay signals
● TYPES OF UMN:
○ Corticospinal Tract: Cortex →
Spinal Cord
○ Corticobulbar Tract: Cortex →
Brainstem
LOWER MOTOR NEURON
● Begin in the spinal cord and go on to innervate muscles and glands throughout the body
● Transmits the signal from the upper motor neuron to the effector muscle to perform a
movement
● Utilize acetylcholine to relay signals
● TYPES OF LMN:
○ Somatic Motor Neurons: located at the brainstem
■ Alpha: innervate extrafusal muscle fibers and are the primary means of
skeletal muscle contraction
■ Beta: innervate both intrafusal and extrafusal muscle fibers
■ Gamma: innervate intrafusal muscle fibers to regulate muscle spindle
sensitivity
○ Branchial Motor Neurons: AKA Special Visceral Neurons; located in the
brainstem and are responsible for forming the LMNs of the cranial nerve nuclei;
They are called "branchial" because they innervate the muscles formed by the
branchial (pharyngeal) arch, which includes muscles innervated by cranial nerves
V, VII, IX, and X.
 ○ General Visceral Motor Neurons: contribute to both the sympathetic and
parasympathetic functions of the autonomic nervous system; Directly involved in
the contractions of the heart, the muscles of the arteries, and other viscera that
are not consciously controlled
GLIAL CELLS
● Astrocytes
○ regulate blood flow and transfer mitochondria to neurons, and supply the building
blocks of neurotransmitters, which fuel neuronal metabolism
● Oligodendrocytes
○ forms the myelin sheath in CNS
● Microglia
○ regulate brain development, maintenance of neuronal networks, and injury repair;
Sweeper of the Nervous System
Definition

● rapidly progressive neuromuscular disease that destroys both UMN and LMN, resulting

in spasticity and diffuse muscular atrophy and weakness (DeLisa)

● Characterized by degeneration of the corticospinal tracts, neurons in the motor cortex

and brainstem, and anterior horn cells in the spinal cord (O’Sullivan)

● Other names:

○ Lou Gehrig’s Disease

○ Charcot’s Disease

○ Motor Neuron Disease

● Main Types:

○ Sporadic ALS: These cases occur randomly, without any known cause, and there

is no family history of ALS .

○ Familial ALS: Affects a small number of people and is thought to be inherited.

Epidemiology

● 4 - 10 cases per 100,000

● Average age of onset: mid-to-late 50s

 ● M>F (1.7:1)

○ After age of 65, gender-related incidence is less pronounced

● Sporadic ALS > Familial ALS

○ 5-10% of FALS is inherited in an autosomal dominant trait

○ 25-40% caused by a defect in the C9ORF72 gene → MC in Europe

○ 12-20% result from mutations in the SOD1 gene → MC in Asia

● Caucasians and non-Hispanics >

● 70-80% limb-onset ALS

● 20-30% bulbar-onset ALS

○ More common among middle-aged women

Etiology

● IDIOPATHIC

● RISK FACTORS

○ Age

○ Family history

■ Autosomal dominant

■ C9ORF72 gene

■ SOD1 gene

○ Smoking

○ Glutamate consumption
PATHOPHYSIOLOGY

Clinical Manifestation

CARDINAL SIGN: Muscle Weakness

CLINICAL HALLMARK: Mixed Palsy

TRIAD:

1. General hyperreflexia

2. Atrophic weakness of hands and forearm

3. Spasticity of legs
UPPER MOTOR NEURON LESION

● Spasticity

● Hyperreflexia

● Clonus

● (+) pathological reflexes

LOWER MOTOR NEURON LESION

● Flaccidity

● Fasciculations

● Muscle atrophy

BULBAR PATHOLOGY

● Spastic bulbar palsy / Flaccid bulbar palsy / Mixed

● Dysarthria

● Dysphagia

● Sialorrhea

● Pseudobulbar affect

● Cognitive impairment

SECONDARY IMPAIRMENTS

● Pain

● Head drop

● Foot drop

● Decreased ROM

● Deconditioning

● Ambulation difficulties

● Impaired postural control and balance

● Depression

● Respiratory impairment
MC CAUSE OF MORTALITY: Respiratory Failure

Diagnosis

The diagnosis of ALS requires the presence of:

1. LMN signs by clinical, electrophysiological or neuropathological examination

2. UMN signs by clinical examination

3. Progression of the disease within a region or to other regions by clinical examination or

via medical history.

4. The absence of:

● Electrophysiological and pathological evidence of other disease that may explain

UMN and LMN signs

● Neuroimaging evidence of other disease processes that may explain the

observed clinical and electrophysiological signs

EL ESCORIAL CRITERIA

CLINICALLY DEFINITE Both UMN and LMN findings in at least 3-4 regions (bulbar,

ALS cervical, thoracic or lumbosacral).

CLINICALLY PROBABLE UMN and LMN signs in two regions, with at least one UMN

ALS finding rostral to the LMN findings.

CLINICALLY PROBABLE, UMN and LMN clinical signs in one region only.

LABORATORY UMN signs alone present in one region and LMN signs defined

SUPPORTED ALS by EMG criteria present in at least two regions.

EMG criteria includes signs of active denervation – fibrillation

potentials and positive sharp waves; and signs of chronic

denervation such as large motor unit potentials and unstable

motor unit potentials.

 CLINICALLY POSSIBLE UMN and LMN signs found together in only one region.

AWAJI-SHIMA CRITERIA

CLINICALLY DEFINITE ALS Clinical or electrophysiologic evidence of LMN and UMN

signs in the bulbar region and at least two spinal regions.

CLINICALLY PROBABLE ALS Clinical or electrophysiologic evidence of LMN and UMN

in at least two regions, with some UMN signs necessarily

rostral to the LMN signs.

CLINICALLY POSSIBLE ALS Clinical or electrophysiologic signs of LMN and UMN

signs in one region.

UMN signs are found alone in two or more regions

LMN signs are found rostral to UMN signs.

SPECIAL TESTS

To check for pathological reflex

● Babinski Reflex

- Stroke lateral aspect of the sole of the foot

- (+) big toe extension and fanning of the four lesser toes

● Gordon’s Reflex

- Squeeze calf muscles firmly

- (+) patient presents with Babinski like response

Differential Diagnosis

AMYOTROPHIC LATERAL SCLEROSIS MULTIPLE SCLEROSIS

SIMILARITIES

● Neurodegenerative disease

● Muscle stiffness

● Characterized by sclerosis

● Affects person’s mobility

M> F>

Physical impairment Mental impairment

Affects motor function Cause sensory disturbance

Prognosis

Age at time of onset has the strongest relationship to prognosis.

→ Less than 35 - 40 years of age at onset – better 5 year survival rates than older individuals

→ Limb-onset ALS have a better prognosis

Poor prognosis

→ Develop ALS >40 y/o

→ Bulbar / pulmonary dysfunction early in clinical course of the disease

→ delay between symptom onset and diagnosis of <6 mos.

Medical Management

● Riluzole

- Glutamate inhibitor, extend survival for patients in the early stages of the disease

- Changes the activity of certain natural substances in the body that affects nerves

and muscles

- Side effects include liver toxicity, asthenia, nausea, vomiting and dizziness

● GABA ANALOG BACLOFEN

- Relax spastic muscles

- Acts to facilitate motor neuron inhibition at spinal levels

● SEROTONIN-MEDIATED TRICYCLIC

- Antidepressants with anticholinergic activity that minimized drooling.

- Help control the symptoms of pseudobulbar effects in ALS

Surgical Management

● Surgery is not a recognized potential ALS risk factor that might modify the onset or

course of ALS

Physical Therapy Managment

Goal: to anticipate the progression of the disease

1. Maintain ROM

2. Avoid contractures

3. Use of soft cervical collar

4. Proper bed positioning

● Restorative Intervention

- Directed toward remediating or improving impairments and activity limitations

- Temporary in the early and middle stages of ALS

 - Late stage is directed solely toward remediation of impairments that result from

other systems pathology

● Compensatory Intervention

- Directed toward modifying activities, tasks, or the environment to minimize

activity limitations and participation restriction

● Preventive Intervention

- Directed toward minimizing potential impairments such as loss of ROM, aerobic

capacity, preventing pneumonia or atelectasis and activity limitations

CERVICAL WEAKNESS

- Mild to moderate – soft foam collar

- Moderate to severe – semirigid or rigid collar

- Combined cervical and upper thoracic weakness – cervical-thoracic orthosis or a sternal

occipital mandibular immobilizer

- Benefit from taking frequent rest periods; supportive seating; high back chairs; tilt in

space or reclining wheelchairs

DYSARTHRIA AND DYSPHAGIA

- Address the patient’s head and trunk control and position in sitting

- Use of chin tuck, prescribed communication devices and need for food inconsistency

SIALORRHEA

- Autonomic Icing

UE MUSCLE WEAKNESS

- Painful shoulder due to subluxation may benefit from a sling

- Splinting of the hand and wrist may be indicated to prevent contractures or to improve

patient’s function

OVERUSE FATIGUE

- Energy expenditure techniques

SHOULDER PAIN

- Caused by several factors:

● Abnormal scapulohumeral rhythm secondary to spasticity or weakness causing

imbalance that may lead to impingement

● Overuse of strong muscles

● Muscle strain

- Interventions

● Modalities

● ROM exercises

● Passive stretching

● Joint mobilization

● Education about proper joint support and protection

RESPIRATORY MUSCLE WEAKNESS

- Patients and caregivers must be taught how to balance activity and rest and educated

about energy conservation techniques, signs and symptoms of aspiration, positioning to

avoid aspiration – upper cervical spine flexion during eating

- Breathing exercises techniques (GLOSSOPHARYNGEAL BREATHING)

LE MUSCLE WEAKNESS AND GAIT WEAKNESS

- AFO - control new impairments and addressing the ankle should be first

- Solid AFOs - good choice for patients who have medial/lateral instability of the ankle with

quadriceps weakness

- Hinged AFOs - allow dorsiflexion and may be appropriate for the patient with adequate

knee extensor strength with mild ankle strength loss

DECREASED MOBILITY

- Transfer boards - used for transfers once the individual is unable to stand

- Transfer belts and swivel cushions or seats

 - Hydraulic or mechanical lift - if an individual cannot perform transfers

- Chair glides or stairway lifts - individuals who live in multilevel homes, but who cannot or

should not climb the stairs

- Manual wheelchair - early or early-middle stage of ALS, used for traveling long distances

as energy conservation technique

- Power wheelchair - can be used as the disease progresses

REFERENCES

● De Lisa, J., Rehabilitation Medicine, 5th edition

● O’Sullivan, Physical Rehabilitation, 7th edition

● https://www.physio-pedia.com/Motor_Neurone#:~:text=Motor%20neurones%20are%20c

ells%20in,the%20way%20to%20the%20toes.

● https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/beta-

motor-neuron#:~:text=Alpha%20motor%20neurons%20(%CE%B1MNs)%20at,innervate

%20both%20intrafusal%20and%20extrafusal

● https://www.mda.org/disease/amyotrophic-lateral-sclerosis

● https://link.springer.com/article/10.1007/s12031-010-9467-1#:~:text=According%20to%2

0the%20dying%2Dback,neuron%20degeneration%20and%20clinical%20symptoms

Ma. Lara Isabel B. Atas, SPT

Freah Zeta L. Cordero, SPT

Batch 2024