ALS - amyotrophic lateral sclerosis SLA - Sclerosi Laterale Amiotrofica Enrico Bonnì

1. ALS
Amyotrophic Lateral
Sclerosis
Enrico Bonnì - 45881 - Erasmus

2. Amyotrophic lateral sclerosis (ALS), also
called Lou Gehrig’s or Charcot’s
disease, is a
neurodegenerative disease characterized by
progressive degeneration of upper (UMN) and
lower (LMN) motor neurons, in the brain and
spinal cord.
They are the cells that control voluntary muscle
activity such as skeletal muscle movement,
breathing, speaking and swallowing.
Definition

3. It was described for the first time by Jean-Martin Charcot in
the 1860s.
It is the most common MotorNeuron Disease, a group of
diseases characterized by the progressive degeneration
and loss of motor neurons (cortical, cranial nerves’ motor
nuclei, anterior horn cells), accompanied by gliosis.

4. • Incidence: 20-30 per 1 million/year
• Sporadic form: 95%
Familial form: 5%, about 10-20% of
them are associated with mutation in
the
Cu Zn Superoxide dismutase 1
(chromosome 21)
Epidemiology

5. • Age of onset: Mean age of onset of sporadic
ALS is 65 years; mean age of onset of familial
ALS ranges from 46-55 years
• M:F 3:2
• 93% of patients in the database are caucasian
• Isolated areas of increased incidence: Kii
peninsula of Japan, Chamorro natives of
Guam

6. • Age
• Family History
• Smoking is the only environmental risk
factor identified that may be considered
“established”
Risk factors

7. • A possible increased risk of ALS in Italian
professional soccer players and NFL players
was reported, but it needs to be confirmed by
other studies.
The balance of the evidence
supports that head trauma in general, including
repetitive head trauma, is not a risk factor for
ALS.

8. • The Etiology of ALS is still unknown.
Etiopathology

9. Cell death's pathway in ALS:
•Oxidative damage
Copper/zinc superoxide dismutase 1 (SOD1) gene encodes an
important antioxidant protein.
His mutation has been seen in 10-20% of familial ALS patients.
•Defects in axonal transport
•Glutamate excitotoxicity
•Aggregation of abnormal proteins
•Mitochondrial dysfunction
•Caspase-mediated cell death (apoptosis)
•Abnormal levels of VE growth factor
affects the capillary density in the spinal cord, meaning that the
nerves and surrounding cells are less irrigated.
The major cause of low VEGF is a mutation
of what is now know as the ALS2 gene.
•Glial cell pathology

10. • Motor nerve degeneration is triggered by the
death of the neuron cell body.
• Death of cell body leads to the degeneration of
the axon (Wallerian degeneration)
• As the axon breaks down, surrounding
Schwann cells catabolize the axon's myelin
sheath and engulf the axon, breaking it into
fragments. This forms
myelin ovoid, containing axonal debris and
surrounding myelin. They are phagocytized by
macrophages.

11. • On muscle biopsy, various stages of atrophy
are noted from this pattern of denervation and
subsequent reinnervation of muscle fibers.

12. • In typical ALS, certain motorneurons are
spared until very late in the disease process:
• In the brain stem: oculomotor, trochlear, and
abducens nerves
• In the spinal cord: the posterior columns,
spinocerebellar tracts, nucleus of Onuf (which
controls bowel and bladder function), and the
Clarke column generally are spared, (Clarke
column can be affected in the familial form of the
disease)

13. The clinical hallmarkof ALS is the mix of
these upperand lowermotorneuron signs.
•Uppermotor neuron signs:
Spasticity, hyperreflexia,
weakness
•Lowermotor neuron signs:
Weakness, muscle wasting,
fasciculations, hyporeflexia, muscle cramps
Sensory neurons are not affected.
minority of patients complains of some numbness
Clinical Features

14. • AMYOTROPHIC: weakness, atrophy, fasiculation
due to denervation of muscles
• LATERAL SCLEROSIS: hyperreflexia, spasticity
due to lateral corticospinal tract degeneration

15. • Asymmetric Weakness is most common sign:
Upper limbs > Lower limbs
Hands > Shoulder girdle muscles
• Bulbarsymptoms is the second most common
presentation: dysarthria or dysphagia
e.g. slurred speech and difficulty chewing and swallowing

16. • Upperlimbs signs and symptoms
difficulty in washing, dropping things, tripping, writing,
pinching
• Lowerlimbs signs and symptoms
Lower extremity: foot drop
Proximal leg weakness: difficulty climbing stairs and
difficulty arising from chairs
• Babinski’s sign positive

17. • Latersigns and symptoms
Progressing muscle weakness
Paralysis
Weight loss
Shortness of breath and Respiratory failure
Dementia (10%)
• Since the nucleus of Onuf is spared,
sphincteric control is normal

18. The clinical standard for diagnosis is the
Revised El Escorial World Federation of
Neurology criteria:
•Evidence of LMN degeneration by clinical,
electrophysiological, or neuropathological
examination
•Evidence of UMN degeneration by clinical
examination
•Progressive spread of symptoms orsigns within a
region or to other regions (The body is divided into
four regions: cranial, cervical, thoracic and
Diagnosis

19. LABstudies
•Nerve conduction studies (NCS):
axonal involvement
•Electromyography (EMG):
mix of acute and chronic denervation features
•MRI

20. • Clinically definite ALS: UMN and LMN signs in at least 3 body
segments
• Clinically probable ALS: UMN and LMN signs in at least 2
body segments with some UMN signs in a segment above the
LMN signs
• Clinically probable, laboratory-supported ALS: UMN and LMN
signs in 1 segment or UMN signs in 1 region coupled with
LMN signs by electromyography (EMG) in at least 2 limbs
• Clinically possible ALS: UMN and LMN signs in 1 body
segment, UMN signs alone in at least 2 segments, or LMN
signs in segments above UMN signs
• Clinically suspectedALS (carried forward from the original El
Escorial criteria): Pure LMN syndrome with other causes of
LMN disease adequately excluded

21. Even with all this technology ALS is
extremely difficult to diagnose.
This is because many diseases mimic signs
of ALS.
Physicians must exclude all treatable
disease before to diagnose ALS.
Differential Diagnosis

22. • OtherMotorNeuron Diseases
• Primary lateral sclerosis
(UMN only)
• Progressive muscular atrophy
(LMN only)
• Progressive bulbar palsy
• Neuropathies
• GB, CIDP
• Myopathies
• PM, inclusion body myositis
• NMJunction
• Myasthenia gravis
• Neurodegenerative Diseases
• Parkinson’s, Progressive
Supranuclear Palsy, MS
• Malignancy
• Primary/mets CNS
• Motor neuron syndromes with
MM, Lymphoma, lung, breast
• Toxic Exposure
• EtOH, heavy metals
• Endocrine
• TSH, adrenal, pituitary
• Infectious
• HIV, CMV

23. • ALS is a progressive disorder with a linear
clinical course: no remissions or
exacerbations
• The life-threatening aspects of ALS are
neuromuscularrespiratory failure and
aspiration pneumonia
• Survival: about 5 years after diagnose
but it’s variable: 50% live 3-
4 or more years, 20% live 5 or more years,
10% live 10 or more years
Progression and Prognosis

24. Treatment
RILUZOLE
•The only available medications for the
treatment
•Glutamate Inhibitor
•Compared with placebo, riluzole may
prolong median tracheostomy-free survival
by 2-3 months in patients younger than 75
years with definite or probable ALS who have
had the disease for less than 5 years and
who have a forced vital capacity (FVC) of
greater than 60%.

25. • The principal clinical side effects some patients
with riluzole may experience are stomach upset
and asthenia (lack of energy).
These problems resolve if
the medication is discontinued.
• Some patients on riluzole develop abnormal liver
function test results or neutropenia.
Serum levels of aminotransferases
should be measured before and during riluzole
therapy, with ALT levels being evaluated every
month during the first 3 months of treatment, every
3 months during the remainder of the first year,
and periodically thereafter.

26. SUPPORTIVE TREATMENT
TRIHEXYPHENIDYL or AMITRIPTYLINE may be
prescribed for people with problems swallowing their
own saliva (sialorrhea)
Limb stiffness can be treated with the antispasticity
agents BACLOFEN (Lioresal) and TIZANIDINE
(Zanaflex).
For treatment of depression, selective serotonin
reuptake inhibitors (SSRIs)

27. Dysphagia poses a risk for aspiration of food,
liquids or secretions with resultant pneumonia
and may also leads to malnutrition and
dehydration.
Symptoms can be minimized in patients who
choose gastrostomy tube insertion with
aggressive management of secretions.

28. Progressive neuromuscularrespiratory failure
is the most common cause of death in ALS.
Noninvasive positive pressure ventilation can
prolong survival up to 20 months.
Some patients choose tracheostomy and
permanent ventilation – it is possible to
maintain patient alive for years (in locked-in
syndrome).

29. Ice Bucket Challenge is an activity involving
dumping a bucket of ice water on someone's
head to promote awareness of the disease
amyotrophic lateral sclerosis and encourage
donations to research. It went viral on social
media during July–August 2014.
On August 29, the ALS Association announced
that their total donations since July 29 had
Ice Bucket Challenge

30. • Harrison's Principles of Internal Medicine, 19th
Edition
• “Motor Neuron Diseases” presentation
Department of Developmental Neurology, Chair of Neurology,
Medical University of
Gdansk (MUG)
• www.emedicine.medscape.com/article/1170097
• www.en.wikipedia.org/wiki/Ice_Bucket_Challen
ge
• “Amyotrophic Lateral Sclerosis ” presentation
Anthony El Khoury, Student Trainer at GC LAU Model United
References

31. Dzi kuje za uwagę ę
Zingaro Nature Reserve, Sicily