Motor neuron disease and amyotrophic lateral sclerosis
In this post we’ll break down the major types of MNDs, compare their clinical features and highlight points crucial for competitive exams like NEET PG, INI-CET, and FMGE. Core issue is combination of UMN and LMN lesion findings coexistent in a same patient for ALS. Physicist Stephen hawking was the longest living survivor of this fatal disorder that ultimately causes demise due to diaphragmatic paralysis. As bonus tip learn differences between AIDP and CIDP in 2 minutes at the bottom of this article.
Comparison of Major Motor Neuron Disease
| Disease | UMN involvement | LMN involvement | Key features | Onset & Progression | Age of Onset | Prognosis |
| Amyotrophic lateral Sclerosis (ALS) | √ | √ | Mixed signs: spasticity + fasciculations; bulbar signs common | Gradual onset, relentless progression | 40-70 years | Fatal within 3-5 years ( respiratory failure) |
| Primary Lateral Sclerosis | √ | X | Pure UMN signs: spasticity, hyperreflexia, Babinski sign: no fasciculations | Very slow progression | >50 years | Relatively benign |
| Progressive muscular Atrophy (PMA) | X | √ | Pure LMN signs; muscle wasting, fasciculations, flaccid weakness | Gradual | 30-60 years | Better than ALS but can evolve into ALS |
| Spinal muscular Atrophy (SMA) | X | √ | Symmetrical LMN weakness, hypotonia, tongue fasciculations (esp. in infants) | Depends on type (infantile to adult) | Infancy to adulthood | Varies (SMA type I is fatal in infancy) |
| Progressive Bulbar Palsy | √ (bulbar UMNs) | √ (bulbar LMNs) | Dysarthria, dysphagia, tongue atrophy, emotional lability | Often progresses to ALS | 40-70 years | Poor |
| Pseudobulbar Palsy | √ | X | Dysarthria, dysphagia, emotional lability, but no tongue wasting or fasciculations | Often associated with bilateral stroked / MS | Older adults | Variable |
Key Clinical Differences
- ALS (Amyotrophic lateral sclerosis)
- Hallmark: Combination of UMN and LMN signs in multiple regions
- Buzzwords: Fasciculations + spasticity: tongue atrophy; split hand sign
- PLS (Primary Lateral Sclerosis)
- Hallmark: Pure UMN involvement
- Clue: No Fasciculations or muscle wasting
- PMA ( Progressive Muscular Atrophy
- Hallmark: Pure LMN disease
- Buzzwords: Muscle atrophy, areflexia, fasciculations, no spasticity
- May progress to ALS over time.
- SMA (Spinal Muscular Atrophy)
- Genetics: Autosomal recessive, SMN1 gene mutation
- Types:
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- Progressive Bulbar Palsy Vs Pseudobulbar Palsy
- Most common MND: ALS
- ALS Affects both UMN and LMN – a key distinguishing feature
- Fasciculations + spasticity: Think ALS
- Tongue fasciculations in infants: Think SMA type I
- No sensory involvement is typical in MNDs.
- Frontotemporal dementia may coexist with ALS (especially C9 or F72 mutation)
- Riluzole is the only FDA – approval drug for ALS – prolongs survival by ~3 months.
- Risdiplam for SMA
- Type: Oral SMN2 splicing modifier
- Mechanism: Increases production of functional SMN protein via enhanced SMN2 splicing
- Route: Oral syrup taken daily
- Age: Approved for infants (>2 months), children, and adult
- Gene therapy for SMA (Type I) with nusinersen and onasemnogene abeparvovec has revolutionized prognosis in children.
- Edaravone has been added as a treatment option in some ALS cases.
| Feature | Progressive Bulbar | Pseudobulbar |
| Site | CN IX – XII (LMN) | UMN to bulbar nuclei |
| Tongue | Atrophy, fasciculations Small spastic, no atrophy | |
| Reflexes | Absent gag reflex | Exaggerated jaw jerk |
| Emotional lability | Present | Present |
| Association | May be variant of ALS | Often bilateral strokes /MS |
Important Exam Points
Recent Advances
Bonus Tip
Comparison: AIDP vs CIDP
| Feature | AIDP (Acute Inflammatory Demyelinating Polyradiculoneuropathy) | CIDP (chronic Inflammatory Demyelinating Polyradiculoneuropathy) |
| Full form | Acute inflammatory demyelinating polyradiculoneuropathy | Chronic Inflammatory Demyelinating Polyradiculoneuropathy |
| Type | Most common variant of GBS | Chronic form |
| Onset | Acute (subtype of GBS) | Chronic (≥ weeks) |
| Progression | Rapid (Similar to GBS) | Slowly progressive or relapsing |
| Weakness | Ascending symmetric | Similar but slower, often proximal and distal |
| Reflexes | Absent or decreased | Absent or decreased |
| CSF | Same as GBS | Same ( mildly elevated protein, low WBC) |
| Nerve Conduction | Demyelinating | Demyelinating |
| Treatment | IVIG or plasmapheresis | Steroids IVIG, plasmapheresis (long -term) |