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MND refers to a spectrum of disorders characterized by degeneration of upper motor neurons (UMNs) in the motor cortex and/or lower motor neurons (LMNs) in the brainstem and spinal cord, resulting in progressive motor dysfunction.

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https://www.youtube.com/watch?v=dg_DntAnU8M

Classification

Subtype UMN Involvement LMN Involvement Typical Age Key Features
‣ Yes Yes 40–70 yrs Mixed UMN and LMN signs
‣ Yes No >40 yrs Slowly progressive spasticity
‣ No Yes 30–60 yrs Pure LMN signs
‣ Yes (bulbar) Yes (bulbar) Variable Dysarthria, dysphagia, emotional lability
‣ No Yes Infancy to adult Genetic, symmetric proximal weakness

Pathophysiology

![Schematic hypothesis of upper and lower motor neuron degeneration, underlying symptom development in MND. (A) Motor neuron degeneration starts with a focal site of onset in the brain and spinal cord, leading to regional symptoms. (B) From this focal site of onset, spread of disease is guided by axonal connectivity to highly connected regions of the neural network. For the upper motor neuron, this involves early interhemispheric spread via the corpus callosum; at the level of the spinal cord, disease spreads to the contralateral site of the spinal segment. The result is a pattern of symptom development with subsequent symptoms in the contralateral side of the body, both in upper and lower motor neuron phenotypes. (C) Neurodegeneration continues to adjacent regions of the motor cortex and spinal cord, reflected by generalization and progression of muscle atrophy and weakness.

Patterns of symptom development in patients with motor neuron disease. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. Published online 2018. doi:https://doi.org/10.1080//21678421.2017.1386688](attachment:dbbaf101-13bf-4357-8d1b-b2fa98c4dc93:iafd_a_1386688_f0002_c.jpg)

Schematic hypothesis of upper and lower motor neuron degeneration, underlying symptom development in MND. (A) Motor neuron degeneration starts with a focal site of onset in the brain and spinal cord, leading to regional symptoms. (B) From this focal site of onset, spread of disease is guided by axonal connectivity to highly connected regions of the neural network. For the upper motor neuron, this involves early interhemispheric spread via the corpus callosum; at the level of the spinal cord, disease spreads to the contralateral site of the spinal segment. The result is a pattern of symptom development with subsequent symptoms in the contralateral side of the body, both in upper and lower motor neuron phenotypes. (C) Neurodegeneration continues to adjacent regions of the motor cortex and spinal cord, reflected by generalization and progression of muscle atrophy and weakness.

Patterns of symptom development in patients with motor neuron disease. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. Published online 2018. doi:https://doi.org/10.1080//21678421.2017.1386688

Clinical Features

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MNDs lead to muscle weakness, atrophy, and eventually paralysis, while sparing sensory function in most forms.

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Prototypical ALS features:

System Findings
UMN signs Spasticity, hyperreflexia, clonus, extensor plantar response
LMN signs Muscle wasting, fasciculations, weakness, hypotonia
Bulbar involvement Dysarthria, dysphagia, tongue fasciculations, pseudobulbar affect
Respiratory Orthopnea, hypoventilation, diaphragmatic weakness
Cognition Up to 50% develop frontotemporal dementia (FTD)
Sensation Typically preserved

Revised El Escorial Criteria (ALS)

Diagnosis based on clinical, EMG, and exclusion of mimics:

Classification Criteria
Definite ALS UMN + LMN signs in ≥3 regions
Probable ALS UMN + LMN signs in ≥2 regions
Possible ALS UMN + LMN in one region, or UMN in ≥2 regions

Differentiating features:

Feature ALS PLS PMA
UMN signs Present Present Absent
LMN signs Present Absent Present
Progression Rapid Slow Variable
Bulbar symptoms Common Late Uncommon
Survival 3–5 years >10 years Better than ALS