Do Amyotrophic Lateral Sclerosis (ALS) patients typically present with combined Upper Motor Neuron (UMN) and Lower Motor Neuron (LMN) signs?

ALS Typically Presents with Combined Upper and Lower Motor Neuron Signs

Yes, ALS patients typically present with combined upper motor neuron (UMN) and lower motor neuron (LMN) signs, which is a hallmark diagnostic feature of the disease. 1, 2

Clinical Presentation of ALS

• ALS is characterized by progressive degeneration of both upper and lower motor neurons in the brain and spinal cord along the corticospinal tracts 3, 1
• Patients typically present with hypertonicity and hyperreflexia (signs of upper motor neuron degeneration) along with muscle fasciculations, weakness, and atrophy (signs of lower motor neuron degeneration) 3, 2
• This combined UMN and LMN involvement is a defining characteristic that helps distinguish ALS from other neurodegenerative conditions 4
• The disease represents approximately 85% of all motor neuron disease cases, with 85-90% of cases being sporadic 3, 1

Diagnostic Criteria

• The diagnosis of ALS requires evidence of both UMN and LMN signs on neurological examination 4
• Electromyography (EMG) and nerve conduction velocity studies are key tests in diagnosing ALS, particularly for confirming LMN involvement 3, 5
• According to the Awaji criteria, EMG findings should have equivalent weight to clinical manifestations to indicate LMN involvement 5
• Diagnostic criteria require a history of slowly progressive motor symptoms with clear spread through the body and exclusion of other disorders 4

Regional Involvement and Progression

• ALS can present with different regional involvement patterns:
  • Bulbar onset (affecting speech and swallowing muscles first) 6
  • Spinal/limb onset (affecting extremities first) 6, 2
• In early disease, approximately 25% of patients have clinical involvement of 1 region, 42% of 2 regions, and 33% of 3 regions 5
• EMG often reveals LMN involvement in clinically unaffected regions, confirming the widespread nature of the disease even in early stages 5

Atypical Presentations

• While combined UMN and LMN signs are typical, there are atypical forms of ALS with predominant involvement of either UMN or LMN systems 2:
  • Primary Lateral Sclerosis (PLS): early and predominant UMN involvement 2, 7
  • Progressive Muscular Atrophy (PMA): early and predominant LMN involvement 2
  • UMN-dominant ALS: predominantly UMN signs but with minor EMG denervation or LMN signs 8
• These atypical forms often progress to develop signs of the other motor neuron system over time 8, 7
• UMN-dominant ALS patients typically have a different pattern of disability progression and longer survival compared to classic ALS 8

Diagnostic Challenges

• The heterogeneous presentation of ALS can make diagnosis challenging, requiring a systematic approach 4
• MRI is primarily used to exclude other conditions rather than confirm ALS 3, 1
• Common MRI findings include abnormal T2/STIR signal in the anterior horns of the spinal cord ("snake eyes" appearance) and abnormal T2/FLAIR signal in the corticospinal tracts 3, 1
• Features at baseline most suggestive of eventual LMN signs include focal muscle weakness or bulbar onset 7

Clinical Course and Prognosis

• Median survival is typically 3-4 years after symptom onset, though this varies with presentation type 3, 1
• Bulbar onset ALS generally has a shorter life expectancy compared to limb onset 6
• Progressive weight loss, reduced forced vital capacity, and increasing limb weakness predict the development of more prominent LMN dysfunction over time 7