Chapter 5

AMYOTROPHIC LATERAL SCLEROSIS

1 Elie Tabcharany M.D.

 Definition
 Amyotrophic lateral sclerosis (ALS) is a disorder that is
generally recognized as an adult-onset progressive motor
neuron disease.

 “la sclérose latérale amyotrophique,” a disorder of muscle

wasting (amyotrophy) and gliotic hardening (sclerosis) of the
anterior and lateral corticospinal tracts involving both upper
and lower motor neurons.

2 Elie Tabcharany M.D.

 Definition
 It is the most physically devastating of the neurodegenerative
diseases.

 Peripheral nerve changes result in muscle fiber atrophy or

amyotrophy.

 The resulting weakness causes profound limitation of

movement.

3 Elie Tabcharany M.D.

 Risk Factors
 Familial ALS (FALS) is an inherited autosomal dominant
trait.

 It occurs in 5% to 10% of all ALS cases.

 The identification of at least one additional family member

with ALS in successive generations is essential for the
diagnosis of FALS.

 It is characterized by an early onset.

4 Elie Tabcharany M.D.

 Risk Factors
 Chronic intoxication with heavy metals, such as lead or
mercury, has been suggested as an etiologic agent, but there
still does not seem to be a clear cause.

 A chemical balance: having higher levels of glutamate

predisposes to ALS.

 ALS occurs predominantly in men.

5 Elie Tabcharany M.D.

 Pathogenesis
 The pathologic hallmarks of ALS are the degeneration and
loss of motor neurons, with astrocytic gliosis and microglial
proliferation in the presence of intraneuronal inclusions in
degenerating neurons and glial cells.

 Upper motor neuron cell loss occurs in the motor cortex,

with loss of frontotemporal cortex, hippocampus,
thalamus...

 There is loss of lower motor neuron axons in the brainstem

and spinal cord.

6 Elie Tabcharany M.D.

 Pathogenesis
 Diffuse and patchy loss of myelin appears in all areas of the
spinal cord except the posterior columns, allowing for
preservation of sensation.

 The death of the peripheral motor neuron in the brainstem

and spinal cord leads to denervation and atrophy of the
corresponding muscle fibers.

 There is remarkable selectivity of neuronal cell death,

involving motor neurons of the brainstem and spinal cord
with relative sparing of the oculomotor nuclei.

7 Elie Tabcharany M.D.

 Clinical Manifestations
 The first symptoms of ALS is things like cramps, weakness,
difficulty chewing and swallowing, and tight muscles.

 As the disease gets stronger the symptoms start to spread out

through your whole body.

 To be diagnosed with ALS, you have to have signs with the

upper and lower motor neuron damage.

8 Elie Tabcharany M.D.

 Clinical Manifestations
 Eventually the disease will become so bad that
people can’t stand or walk.

 Over time people will start having problems with

breathing and soon they can’t breath at all on
their own.

9 Elie Tabcharany M.D.

 Prevention
 There is no prevention that we know for ALS because we
don’t know the cause of the disease.

10 Elie Tabcharany M.D.

 Treatments and cures
 There is no cure for ALS but there are treatments.
 A medicine called Rilutek helps slow down the disease.
 It decreases glutamate levels.

11 Elie Tabcharany M.D.

 ALS Ice Bucket Challenge
 The ALS Ice Bucket Challenge
is a challenge used to raise
awareness for people with ALS.

 To participate you record

yourself dumping a bucket of
ice water over your head.

 The reason for dumping ice

cold water over your head is to
know what having ALS feels
like for a split second.

12 Elie Tabcharany M.D.