Motor neuron diseases

Question 1

What are motor neuron diseases?

Answer 1

One classification of neuromuscular diseases

Question 2

What are three main groups of motor neuron diseases?

Answer 2

• SMA (Spinal muscular atrophy)
• SMAJ (Spinal muscular atrophy, Jokela’s type)
• ALS (Amyotrophic lateral sclerosis)

Question 3

What is ALS?

Answer 3

Most common motor neuron disease in adults. It is characterized by progressive loss of motor neurons that controls voluntary muscles in spinal cord, brain stem and cortex.
- ALS results in muscle atrophy and paralysis of limb and bulb musculature. Death due to respiratory and heart muscular weakness after 3-5 years after diagnosis.

Question 4

What are mechanism of ALS?

Answer 4

• Mutations in three genes covers 25% of familial ALS. These genes are SOD1, FUS, TDP43.
• There are several pathological mechanism (mitochondrial defects, oxidative stress, protein misfolding etc) identified but still mechanism behind ALS is uknown.
• Impaired proteostasis -> accumulation of damaged proteins (impaired DNA repair)

Question 5

Are men more affected?

Answer 5

yes

Question 6

Is ALS inherited?

Answer 6

• Total heritability is ~21%
• Autosomal dominant, autosomal recessive or X-chromosomal inheritance
• Genes:c9orf72, SOD1 main genes

Question 7

How is ALS diagnosed?

Answer 7

• No definitive diagnosis test
• Confirmation of diagnosis is based on clinical findings, electromyopathy results and exclusion of mimics
• Identification of upper and lower motor signs

Question 8

Is there any treatment for ALS?

Answer 8

• No specific treatment
• riluzore prolong survival, do not help with symptoms. Multiple mechanism, e.g. glutamate release blocker
• Edaravone (suppress oxidative stress)

Question 9

How is SMA characterized?

Answer 9

Loss of motor neurons in spinal cord -> loss ability to walk, breath, eat.

• Neurodegenerative disease
• Progressive muscle weakness and atrophy

Question 10

Is there any treatment for SMA?

Answer 10

-Nusinersen (can be used in childhood severe forms). This medicine modulates the mRNA transcript (of SMN2) to include exon 7.

• Rehabilitation: Individual rehabilitation plan with physiotherapist and/or occupational therapist
• Evaluating of walking aids and special consultation (including orthopedics)

Question 11

How are the SMAs classified?

Answer 11

Based on the age of onset and clinical course (SMA0, SMA1, SMA2…). SMA IV occurs in adulthood, dont affect in life span. Approximately 60% of infants have SMA1 type.

Question 12

What mutation in which gene happens in SMAJ?

Answer 12

• Mutation c66v in the gene CHCHD10

- 64% males