Amyotrophic Lateral Sclerosis
Autoimmune reaction
- AKA: Lou Gehrig’s Disease
- Most common & devastatingly fatal motor
neuron disease among adults
- Characterized by the degeneration and loss
of motor neurons in the spinal cord,
brainstem and brain
- Considered as UMNL and LMNL
Types
1. Limb-onset
- distinctive weakness (extensors in UE, flexors
in LE)
- Brachial-manual amyotrophy is more
common than crural type
2. Bulbar-onset
- CBT degeneration to CN 5, 7, 9, 10, 11, 12
(spared CN 3, 4, 6)
Epidemiology
- Age of onset: mid to late 50’s
- Gender: Men>Women
- 5% to 10% of individual inherited the disease
as an Autosomal Dominant trait (Familial
ALS)
- 20% result of one of >100 mutations in
superoxide dismutase 1 (SOD1)
- Around 70-80% individuals develop limb-
onset ALS,
- Around 20-30% develop bulbar-onset ALS
with initial involvement in bulbar muscles
- Bulbar onset ALS more common in middle-
aged women
Etiology
1. Superoxide Dismutases
- A group of enzymes that eliminate oxygen
free radicals that although products of
normal cell metabolism
- SOD1 (a gene in chromosome 21) undergo
mutation with adult-onset FALS; this mutant
SOD-1 protein may have toxic properties
that cause motor neurons to die
2. Glutamate
- An excitatory neurotransmitter
- Excess glutamate may trigger a cascade of
events that can lead cell to undergo
apoptosis
3. Clumping of neurofilaments proteins into
spheroids in the cell body and proximal
axon
- One of the histopathological characteristics
of ALS
4.
- Serum factor & antibodies to calcium
channels toxic to anterior horn motor
neurons with ALS
5. Neurotrophic Factors and other
neurodegenerative disorders
6. Other theories (Exogenous/environmental
factors, apoptosis and viral infections)
Pathophysiology
- neuronal loss, gliosis, and vacuolation of
precentral gyrus, BS & SC (i.e. CST)
- Aα motor fibers are more affected than Aγ
fibers Motor neurons contain Bunina or
Hirano bodies
- As your motor neuron degenerate = they
cannot control the muscle fibers they
innervate
- Healthy intact axons can sprout and
reinnervate partially denervated muscle to
assume the role of the degenerated motor
neuron and preserving the strength and
function early in the disease
- Reinnervation can compensate for
progressive degeneration until motor unit
loss is about 50% Commented [JPLRE1]: A gene that encodes the copper-
- As ALS progress, reinnervation cannot zinc superoxide dismutase enzymes
compensate for the rate of degeneration
and a variety of impairments will develop.
- The signs and symptoms of ALS spread
locally within a region (e.g. bulbar, cervical,
thoracic, lumbosacral) before moving to
other regions
- Caudal to rostral spread within SC and
spread from cervical to bulbar region
appears to occur faster than rostral to
caudal spread within SC.
Stages of ALS
- Stage 1: Early disease, mild focal weakness,
asymmetrical distribution; symptoms of hand
cramping and fasciculations
- Stage 2: Moderate weakness in groups of
muscles, some wasting of muscles; modified
independence with assistive device
- Stage 3: Severe weakness of specific
muscles, increasing fatigue; mild to
moderate assistance functional limitations,
ambulatory
- Stage 4: Severe weakness and wasting of
LE’s; mild weakness of UE; moderate
 assistance and assistive device required;
W/C user
- Stage 5: Progressive weakness with
deterioration of mobility and endurance,
increased fatigue, moderate to severe
weakness of whole limbs and trunk;
spasticity, hyperreflexia; loss of head control;
maximal assist
- Stage 6: Bedridden; dependent ADL’s, FMS,
progressive respiratory distress
Clinical Manifestation
- asymmetric UMN/LMN S/Sx, initially distal &
bulbar mm
- Muscle wasting does not reflect significant
weakness, relative preservation of power
early in the illness
- (+) “cadaveric”/”skeletal” hand: dorsal
interosseus spaces become hollowed d/t
atrophy of intrinsics
- Head lolling and camptocormia (forward
bending of neck and trunk)
- Generalized hyperreflexia, slight spasticity
(extreme spasticity is rarely seen)
- Babinski & Hoffman signs are variably
present
- Death is d/t respiratory failure, most
succumb ~ 6 years
- Spared: ocular mm, bowel & bladder
(Onuf’s nucleus), sensation
- Autonomic dysfunction common in about
1/3 of patients
- Pain d/t spasticity, cramping, postural stress
syndrome, joint hypomobility or instability
- Respiratory impairments weakness>paralysis,
nocturnal difficulty; exertional dyspnea,
accessory muscle use; paradoxical
breathing, ventilator dependent, poor
cough, clearance of secretion
- Typical sparing of bowel and bladder
function
Poor Prognosticating Factor
- Female
- Old
- Bulbar symptoms at onset
- >LMNL
- Rapid progression
Predictors of Survival
- Age of onset (younger is better)
- Severity of onset
- Pulmonary function
- Abnormal sniff test correlates with poor
survival
El Escorial Criteria in Diagnosing ALS Commented [JPLRE3]: Requisites:
UMN, LMN, Progressive spread (regions: bulbar, cervical,
Variants of ALS thoracic, lumbar)
1. Familial ALS – AD, M=F, SOD1 gene mutation, Suspected ALS: LMN signs only > or = 1 region; UMN signs
S/Sx do not usually differ with nonfamilial types, only > or = 1 region
though earlier onset and shorter survival
2. Juvenile Inclusion Body ALS – <25 y/o, AD (ch 9, Possible ALS: LMN + UMN 1 region
senataxin gene) or AR (ch 2q33, alsin gene, ch Probable ALS Lab supported: LMN + UMN 1 region or UMN
15q – predominantly LMN) forms, slower > or = 1 region; EMG (Acute denervation > or = 2 limbs)
progression Probable ALS: LMN+UMN 2 regions
Definite ALS: LMN+UMN 3 regions
3. ALS-Plus syndromes
 ALS with frontotemporal dementia – AD, FUS
gene, frontal & anterior temporal
degeneration
 Western Pacific ALS-parkinsonism-dementia Commented [JPLRE2]: According to O’Sullivan
complex – hallmark: aberrant tau protein (2014),initial mm weakness occurred in isolated muscles,
4. Groote Eylandt Motor neuron disease – most often distally and is followed by progressive weakness
Australian aborigines and activity limitation
5. Post-encephalitic (encephalitis lethargica) ALS
6. Hemiplegic/Mills variant – affecting the arms Muscle weakness is considered as a cardinal sign of ALS
and leg on same side, first with spasticity, then
with some degree of amyotrophy
Medications
- Rilozule Commented [JPLRE4]: inhibits presynaptic release of
glutamate
Rehab Stages of ALS
1 – independent ADL  gen conditioning
2 – difficulty ADL  adaptive equipment
3 – ambulatory but with marked weakness 
consider w/c mobility, use of cervical collar
4 – severe LE weakness, mild UE weakness  w/c
mob
5 – assistance in all ADL
6 – ADL dependent
Things to consider
- Overwork of the muscles (also eccentric
exercises) leading to fatigue, cramps, and
dyspnea should be avoided. Watch for
DOMS.
- Aerobic and resistance (mild-mod intensity)
exercise for 15 mins.
- Supplemental O2 suppresses respiratory drive
and can worsen symptoms and lead to
respiratory arrest and should only be used
for palliation of symptomatic hypoxia.
- Noninvasive ventilation (NIV) is preferred
early, indicated if FVC <50% and maximum
inspiratory pressure (MIP)≤60 cm H2O or a
PaCO2 of ≥45 mm Hg.
- Refer for gastrotomy procedures (PEG or RIG
tubes) to supplant oral feeding, when FVC
<50%
Examination for ALS
- Hx: varied pattern of onset
- VS, respiratory function
- CN testing; especially lower cranial nerves
(CN VII, IX, X, XI, XII)
- Motor function
a. Examine for atrophy, widespread weakness;
a symmetrical distribution, muscle cramping
and muscle twitching
b. Examine for spasticity and hyperreflexia
c. Coordination tests: manual skills
- Sensory function
- Gait: timed walk (10-m walk test)
- Functional status: monitor closely for fatigue,
persistent weakness following exercise or
activity; e.g. keep activity diary
- ALS functional rating scale (ALSFRS):
assessed disease progression and function
across 10 functional categories; scored 0
(loss of function) to 4 (normal function); 40
maximal score
PT Goals, outcomes and interventions
1. Maintain respiratory function
2. Provide for nutritional needs
3. Prevent indirect impairments
4. Provide moderate exercise program
5. Teach energy conservation activity, pacing
techniques (e.g. balance activity with rest)
6. Maintain maximal functional independence;
provide appropriate AD, W/C or
environmental adaptations
7. Symptomatic tx of pain, spasms and
spasticity
Progressive Bulbar Palsy
- Sporadic
- Dominant S/Sx involve mm of the jaw, face,
tongue, pharynx and larynx, give rise to an
early defect in articulation, voice is usually
modified by a combination of atrophic and
spastic weakness, ocular muscles are spared
- Jaw jerk may be present or exaggerated at
a time when the muscles of mastication are
markedly weak, may present (+) “bulldog”
reflex (jaw snaps shut involuntarily, elicited
by attempts to open the mouth)
- Progressive, death within 2-3 years of onset
- Mx: supportive
UMN Disorders
Primary Lateral Sclerosis
- rare, nonfamilial, slow progression, adult (20-
60 y/o), M=F
- Pathology: precentral gyrus (pyramidal cells)
atrophy, CST (& CBT) degeneration
- S/Sx: initially asymmetric, LEUE bulbar,
spasticity predominating over weakness
- Mx: supportive
Hereditary/Familial Spastic Paraplegia
- AKA: Strumpell-Lorrain disease
- Mostly AD
- Pathology: CST degeneration in SC
- Pure HSP presents with symmetric spastic
paraplegia, sensory and other nervous
functions are intact
 Variants:
 HSP with ataxia (Ferguson Critchley syndrome)
 HSP with extrapyramidal signs
 HSP with optic atrophy (Behr syndrome, optic
atrophy-ataxia syndrome)
 HSP with macular degeneration (Kjellin
syndrome)
 HSP with developmental delay or dementia
 HSP with polyneuropathy
 HSP with distal muscle wasting (Troyer
syndrome)
Lathyrism
- Excessive consumption of chickling pea
(lathyrus sativus) assoc with toxic agent β-N-
oxalylamino-L-alanine Commented [JPLRE5]: May require airway clearance
techniques, cough facilitation, DBT, chest stretching,
Viral infectious disorders suctioning incentive spirometry, long-term mechanical
- HIV-related myelopathy – vacuolar ventilation
myelopathy d/t vacuolization of myelin Commented [JPLRE6]: Assist in mx of dysphagia, may
sheath with relative preservation of axons require NGT or percutaneous gastromy in later stages
- Human T-cell lymphotropic virus type 1-
Commented [JPLRE7]: Maintain activity levels as long as
associated myelopathy – AKA tropical
possible, PROME, positioning, skin care
spastic paraparesis, slowly progressive, starts
after 30 y/o Commented [JPLRE8]: a. Prevent further
deconditioning and disuse atrophy while avoiding
overwork damage in weakened, denervated muscle
b.Mild aerobic activities (swimming, walking, stationary
bike
c.As disease progress, replace resistance ex. With fxnal
training activities
d.Monitor fatigue closely