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JOURNAL READING

Amyotrophic Lateral
Sclerosis

Dosen Pembimbing : dr. Agus Yudawijaya, Sp. S


Disusun Oleh :
I Gusti Agung Ayu Gita L.S 1765050161

Kepaniteraan Departemen Ilmu Penyakit Saraf


Fakultas Kedokteran Universitas Kristen Indonesia
Periode 9 Desmber 2019 – 18 Januari 2020
JAKARTA
DEFINITION
• Amyotrophic Lateral Sclerosis (ALS) is characterised by progressive
degeneration of upper (UMN) and lower (LMN) motor neurons in
the brain and spinal cord.

• ALS is the most common form of motor neuron disease (MND)

• ALS begins in limb or bulbar muscles and then spreads to


contiguous and eventually respiratory, myotomes. Survival ranges
from months to decades, but is usually less than 3 years from when
symptoms first appear.
DEFINITION
• Amyotrophic lateral sclerosis (ALS) is a rapidly progressive
neurodegenerative disorder of the human motor system, clinically
characterized by dysfunction of the upper and lower motor neurons,
which forms the basis of diagnosis
ETIOLOGY
• There are no known causes for most patients and no cures.

• Genetic mutations account for some of the 5–10 % of cases that are inherited
(familial ALS [fALS])

• Sporadic ALS (sALS) is thought to have both genetic and environmental influences,
but the principle causes await discovery.

• a prominent event in damaged neurons is aggregation of misfolded


proteininfluence nearby wild type protein to change conformation  a disease
that begins in one area is transmitted widely in the brain
PATHOGENESIS
• Approximately 5–10 % of ALS is familial. Mutations have been
identified in some forms, but the mechanisms by which gene
alterations cause ALS await elucidation.
• The most common genes linked to fALS:
• Superoxide dismutase Cu/Zn cytosolic (SOD1) gene on chromosome 21
• TAR DNA-binding protein 43 (TARDBP),
• fused in sarcoma (FUS/TLS) and
• C9ORF72
• Currently, 15–20 % of fALS cases, mostly autosomal dominant, are
due to one of more than 150 mutations in the SOD1 gene.
PATHOGENESIS
Three opposing theories have been proposed to unravelling ALS
pathogenesis :
• The dying forward hypothesis
• The dying back hypothesis
• The independent hypothesis
PATHOGENESIS
• Mutations in the c9orf72, TDP-43 and fused in sarcoma (FUS)
transporter 2 (EAAT2) result in dysregulated RNA metabolism leading
to abnormalities of translation and formation of intracellular neuronal
aggregates.
• Mutations in the superoxide dismuates-1 (SOD-1) gene increases
oxidative stress, induces mitochondrial dysfunction, leads to
intracellular aggregates, and defective axonal transportation.
Clinical Features and Diagnosis
• The disease affects LMNs in the medulla and anterior horn of the
spinal cord

• The disease affects UMNs in the cerebral cortex.

• The result for patients is progressive muscle weakness  death,


usually from respiratory failure.
Clinical Features and Diagnosis

UMN LMN
• Spasticity, • Fasciculation,
• Hyperreflexia and • Cramps,
• Modest weakness • Muscle atrophy and
• Babinski and hoffmann signs • Weakness
• Emotional lability
Clinical Features and Diagnosis
• ALS begins in the limbs, most often in the arms.

• The first symptoms are usually unilateral and focal.

• Early findings include foot drop, difficulty walking, loss of hand


dexterity or difficulty lifting the arms over the head.

• Eventually, limb function can be lost, dependence on caregivers.


Clinical Features and Diagnosis
• Bulbar-onset disease, often occurring in older women, appears to have worse
prognosis.
• Dysarthria  dysphagia anarthria, drooling and malnutrition.

• An atrophied fasciculating tongue is so characteristic of bulbar ALS that it is virtually


diagnostic of the condition.

• Axial weakness can cause dropped head and kyphosis, features associated with pain
and poor balance

• Eye movements are preserved until advanced stages.


Clinical Features and Diagnosis
• Overt frontotemporal dementia occurs in approximately 15 % of patients

• Changes involve language, judgment, personality, affect and executive function.

• Patients with ALS and dementia have shorter survival, possibly as a result of poor
decision-making ability.

• Depression and anxiety can occur during any stage. When present, emotional
symptoms impair quality of life through poor appetite and sleep, and feelings of
hopelessness.
Clinical Features and Diagnosis
• Morning headache, weakened cough, orthopnoea and exertional
dyspnoea are early respiratory symptoms.

• Later, shortness of breath develops, first during simple tasks such as


dressing and eating, and eventually at rest.
Clinical Insight
• The split-hand phenomenon refers to preferential wasting of the thenar group of
intrinsic hand muscles, namely abductor pollicis brevis (APB) and first dorsal
interosseous (FDI)

• A split hand phenomenon, reffering to prefertential weakness of the APB muscle when
compared to the flexor pollicis brevis

• Split leg and split elbow  specific clinical features of ALS, related to cortical disfunction

• The site of disease-onset ALS, was more likely to be evident in the dominant hand of
upper limb
Management
• Riluzole was developed because it possesses anti-glutamatergic
properties;

• it might act in ALS to reduce exitotoxicity and apoptosis.

• Riluzole slowed progression of ALS


Management
NUTRITION AND GASTROSTOMY
• inadequate nutrition and dehydration become common as ALS
advances. Bulbar muscle weakness and dysphagia, inability to eat
adequately due to arm weakness and hypermetabolism all contribute
to negative calorie balance  The end result is weight loss

• Monitoring weight is the simplest way to assess caloric balance in the


clinic. When positive caloric balance is no longer possible orally, a
gastrostomy is indicated.
Management
VENTILATORY SUPPORT
• As respiratory muscle weakness advances dyspnoea, orthopnoea,
sleep fragmentation, daytime fatigue and morning headaches.
• A weakened cough due to diaphragmatic and bulbar muscle weakness
 excess secretions, poor airway clearance and aspiration.
• The cause of death in ALS is usually respiratory, with approximately 60
% of patients having a predictable gradual decline in function and 35 %
having sudden death.
• Noninvasive ventilation (NiV) is the standard intervention for patients
with respiratory insufficiency.
TERIMA KASIH