❓What❓
- A neurodegenerative disease classically characterized by the presence of both UMN ⊕ LMN symptoms & signs, but with a wide spectrum of presentations owing to differences in body site & nervous system segment of onset, pattern & speed of spread, & degree of UMN vs. LMN dysfunction
- UMN disease refers to symptoms & signs of dysfunction of the central motor pathways of the brain & spinal cord leading to disinhibition of tonically active peripheral nerves, which can present with slowness, incoordination, stiffness, hyperreflexia, spasticity, & pathologic reflexes
- LMN disease refers to symptoms & signs of dysfunction of the peripheral motor pathways from the brainstem or anterior horn cells to the effector muscles leading to muscle denervation, which can present with weakness, atrophy vs. amyotrophy, muscle cramps, & fasciculations
- Importantly, non-motor neurologic symptoms are seen in up to 50% at time of diagnosis, & the presence of distinct phenotypes may represent a single motor neuron disease continuum rather than distinct diseases (see Presentation)
❓Epidemiology❓
Symptoms at Onset
- Most common = asymmetric, progressive limb weakness (~70-80%)
- Least common = bulbar (~20%), respiratory (~1-3%), generalized limb ⊕ bulbar (~1-10%), & axial symptoms
Survival
- Median = 3 to 5 years
❓Presentation❓
- Dyspnea-Fasciculation Syndrome 📳 : describes the syndrome of early respiratory failure due to diaphragmatic weakness despite minimal weakness elsewhere, but with prominent fasciculations on exam
- Primary Lateral Sclerosis 📳 : isolated UMN dysfunction
- Progressive Muscular Atrophy 📳 : isolated LMN dysfunction
- Progressive Bulbar Palsy 📳 : progressive cranial muscle dysfunction (e.g. dysarthria, dysphagia, ↑ jaw jerk reflex, tongue wasting)
- Flail Arm vs. Leg Syndrome 📳 : progressive LMN weakness & wasting predominantly affecting the proximal arm vs. distal leg, respectively
- Hemiplegic ALS 📳 : very rare syndrome with onset in distal leg followed by arm & bulbar regions
- “ALS ⊕” Syndromes 📳 : frontotemporal dementia, cerebellar degeneration, Parkinsonism, supranuclear gaze palsy
❓Diagnosis❓
“Rule-Out”
- The diagnostic pathway to ALS begins by ruling-out mimickers via …
- MRI Spine: assess for cervical myelopathy vs. other myelopathy
- LP: assess for CIDP & CIDP mimickers, Lyme disease, HIV, lymphoma
- TSH, FT4, FT3: assess for thyrotoxicosis
- Myasthenia Gravis Antibodies: if ocular findings present & absent UMN/LMN signs
“Rule-In”
- EMG: may show findings of acute muscle denervation (e.g. fibrillation & positive sharp waves), chronic muscle denervation (e.g. fasciculation potentials representing spontaneous firing of motor units not voluntarily recruited), & reinnervation (e.g. large-amplitude, long-duration, complex MUAPs)
- NCS: sensory & motor nerve conduction studies are most often normal, though CMAP amplitudes may be ↓ in severely atrophic & denervated muscles
📚 References 📚
