Motor Neuron Diseases Overview

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Questions and Answers

Match the following symptoms with their associated disease:

Muscle weakness and atrophy = Amyotrophic Lateral Sclerosis (ALS) Hypotonia = Spinal Muscular Atrophy (SMA) Respiratory problems = Amyotrophic Lateral Sclerosis (ALS) Limited ability to move = Spinal Muscular Atrophy (SMA) Type 1

Match the following types with their descriptions:

Sporadic ALS = Most common form with no known family history SMA Type 2 = Onset between 6-18 months; able to sit but not stand Familial ALS = Genetic mutations contribute to disease SMA Type 4 = Adult-onset; milder symptoms with slower progression

Match the following treatments with their corresponding disease:

Riluzole = Amyotrophic Lateral Sclerosis (ALS) Nusinersen (Spinraza) = Spinal Muscular Atrophy (SMA) Edaravone = Amyotrophic Lateral Sclerosis (ALS) Onasemnogene abeparvovec (Zolgensma) = Spinal Muscular Atrophy (SMA)

Match the following diagnostic methods with the diseases they are used for:

Electromyography (EMG) = Both ALS and SMA Genetic testing for SMN1 = Spinal Muscular Atrophy (SMA) Clinical examination = Amyotrophic Lateral Sclerosis (ALS) MRI to rule out other conditions = Amyotrophic Lateral Sclerosis (ALS) Signup and view all the answers

Match the following definitions with the correct disease:

A progressive neurodegenerative disease affecting motor neurons = Amyotrophic Lateral Sclerosis (ALS) A genetic disorder characterized by degeneration of motor neurons = Spinal Muscular Atrophy (SMA) Muscle cramps and twitching = Amyotrophic Lateral Sclerosis (ALS) Caused by mutations in the SMN1 gene = Spinal Muscular Atrophy (SMA) Signup and view all the answers

Match the following age of onset with the specific type of Spinal Muscular Atrophy:

Before 6 months = SMA Type 1 Between 6-18 months = SMA Type 2 After 18 months = SMA Type 3 Adult-onset = SMA Type 4 Signup and view all the answers

Match the following factors with the disease they are primarily associated with:

Muscle wasting and weakness = Spinal Muscular Atrophy (SMA) Progressive disease affecting speaking and swallowing = Amyotrophic Lateral Sclerosis (ALS) Genetic mutations like SOD1 = Familial ALS Increased SMN protein levels = Nusinersen (Spinraza) Signup and view all the answers

Match the following key features with the correct disease:

Fasciculations = Amyotrophic Lateral Sclerosis (ALS) Decreased muscle tone = Spinal Muscular Atrophy (SMA) Supportive care includes physical therapy = Both ALS and SMA Diagnosis includes muscle biopsy = Spinal Muscular Atrophy (SMA) Signup and view all the answers

What role does the SMN2 gene play in patients with spinal muscular atrophy (SMA) compared to SMN1?

The SMN2 gene partially compensates for the loss of SMN1 by producing SMN protein, but it mainly generates truncated proteins due to the lack of exon 7. Signup and view all the answers

How does the number of copies of the SMN2 gene influence the severity of SMA symptoms?

A higher copy number of the SMN2 gene is generally associated with a milder disease phenotype. Signup and view all the answers

Why can't SMN2 fully compensate for the absence of SMN1 in motor neurons?

SMN2 cannot fully compensate because a majority of its transcripts lack exon 7, resulting in the production of a truncated and less stable SMN protein. Signup and view all the answers

What is the clinical significance of the variations in SMA symptoms among patients with the same SMN2 copy number?

Clinical variations despite similar SMN2 copy numbers highlight the complexity of SMA and indicate other genetic or environmental factors affecting disease presentation. Signup and view all the answers

Discuss the implications of having a positive correlation between SMN2 copy number and phenotype severity in SMA patients?

This correlation implies that interventions aimed at increasing SMN2 expression may lead to improved outcomes and milder disease severity. Signup and view all the answers

Study Notes

Motor Neuron Diseases

Amyotrophic Lateral Sclerosis (ALS)

Definition: A progressive neurodegenerative disease affecting motor neurons in the brain and spinal cord.
Symptoms:
- Muscle weakness and atrophy
- Difficulty speaking (dysarthria) and swallowing (dysphagia)
- Respiratory problems
- Muscle cramps and twitching (fasciculations)
Onset: Typically occurs in individuals aged 40-70 years; can be sporadic or hereditary.
Types:
- Sporadic ALS: Most common form, with no known family history.
- Familial ALS: Genetic mutations (e.g., SOD1, C9orf72) contribute to disease.
Diagnosis:
- Clinical examination
- Electromyography (EMG)
- MRI to rule out other conditions
Treatment:
- Riluzole: Slows progression of the disease.
- Edaravone: Reduces oxidative stress.
- Supportive care: Physical therapy, respiratory support, nutritional management.

Spinal Muscular Atrophy (SMA)

Definition: A genetic disorder characterized by the degeneration of motor neurons in the spinal cord, leading to muscle wasting and weakness.
Types:
- SMA Type 1: Severe form, onset before 6 months; limited ability to move or breathe.
- SMA Type 2: Intermediate form, onset between 6-18 months; able to sit but not stand.
- SMA Type 3: Mild form, onset after 18 months; can walk unaided but may lose function over time.
- SMA Type 4: Adult-onset; milder symptoms with slower progression.
Symptoms:
- Muscle weakness and atrophy
- Hypotonia (decreased muscle tone)
- Difficulty with movement and coordination
Genetics: Caused by mutations in the SMN1 gene, leading to insufficient survival motor neuron protein.
Diagnosis:
- Genetic testing for SMN1 gene mutations
- Electromyography (EMG)
- Muscle biopsy (in certain cases)
Treatment:
- Nusinersen (Spinraza): Antisense oligonucleotide that increases SMN protein levels.
- Onasemnogene abeparvovec (Zolgensma): Gene therapy that delivers a copy of the SMN1 gene.
- Supportive care: Physical and occupational therapy, nutritional support.

Amyotrophic Lateral Sclerosis (ALS)

A progressive neurodegenerative disease impacting motor neurons in both the brain and spinal cord.
Symptoms include muscle weakness, atrophy, dysarthria (difficulty speaking), dysphagia (difficulty swallowing), respiratory issues, muscle cramps, and twitching (fasciculations).
Onset typically occurs in individuals aged 40-70 and can manifest as sporadic or hereditary cases.
Types of ALS:
- Sporadic ALS: Affects the majority with no known family history.
- Familial ALS: Linked to genetic mutations, notably SOD1 and C9orf72.
Diagnosis involves clinical examination, electromyography (EMG), and MRI scans to exclude other disorders.
Treatment options include:
- Riluzole: Medication that slows disease progression.
- Edaravone: Helps reduce oxidative stress.
- Supportive care focusing on physical therapy, respiratory support, and nutritional management.

Spinal Muscular Atrophy (SMA)

A genetic disorder resulting in the degeneration of motor neurons in the spinal cord, causing muscle wasting and weakness.
Types of SMA:
- SMA Type 1: Most severe, onset occurs before 6 months, limited mobility, and breathing capacity.
- SMA Type 2: Intermediate severity with onset between 6-18 months; patients can sit but cannot stand.
- SMA Type 3: Milder form starting after 18 months; patients can walk unaided but may eventually lose function.
- SMA Type 4: Adult-onset with milder symptoms and slower disease progression.
Common symptoms include muscle weakness, atrophy, hypotonia (reduced muscle tone), and coordination difficulties.
The condition is caused by mutations in the SMN1 gene, leading to inadequate survival motor neuron protein levels.
Diagnosis is carried out through genetic testing for SMN1 mutations, electromyography (EMG), and, in some instances, muscle biopsy.
Treatment approaches consist of:
- Nusinersen (Spinraza): An antisense oligonucleotide that enhances SMN protein levels.
- Onasemnogene abeparvovec (Zolgensma): A gene therapy providing a functional copy of the SMN1 gene.
- Supportive care including physical and occupational therapy, as well as nutritional support.

Spinal Muscular Atrophy (SMA) and SMN Genes

Homozygous loss of the SMN1 gene causes spinal muscular atrophy (SMA).
Absence of SMN1 is partially compensated by SMN2, which produces some SMN protein necessary for development.
SMN2 primarily benefits cell types other than motor neurons but does not fully compensate for the loss of SMN1.

Role of SMN2 in SMA

SMN2 is transcribed comparably to SMN1, but many SMN2 transcripts lack exon 7.
Exclusion of exon 7 results in a truncated and less stable SMN protein.
Patients with SMA rely on functional SMN protein produced by residual SMN2 for alpha motor neuron function and survival.

Correlation between SMN2 Copy Number and Disease Severity

There is a positive correlation between the number of SMN2 copies and the severity of the phenotype.
A higher SMN2 copy number typically indicates a milder disease phenotype.
Clinical presentation of SMA varies significantly among patients, even within subgroups categorized by SMN2 copy number.
Discordance occurs between expected phenotype based on SMN2 count and actual clinical outcomes.

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Description

This quiz explores two primary motor neuron diseases: Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA). It covers definitions, symptoms, onset, types, diagnosis, and treatment options for these conditions. Test your knowledge on the critical aspects of these neurodegenerative disorders.