Primary Lateral Sclerosis

Complex MONDO:0018155 Motor Neuron Disease Neurodegenerative Disease

Primary lateral sclerosis is a progressive upper motor neuron disorder with insidious onset and slow progression.

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Pathophysiology

Progressive Upper Motor Neuron Dysfunction

Degeneration of upper motor neurons leads to slowly progressive spasticity and motor impairment without lower motor neuron signs.

Show evidence (1 reference)

PMID:26515619 SUPPORT

"Primary lateral sclerosis is characterized by insidious onset of progressive upper motor neuron dysfunction in the absence of clinical signs of lower motor neuron involvement."

The abstract defines PLS by progressive upper motor neuron dysfunction.

Corticospinal Tract Degeneration

Neuropathology shows degeneration of the primary motor cortex and corticospinal tracts with relative preservation of lower motor neurons.

Show evidence (1 reference)

PMID:33602010 SUPPORT

"Degeneration of the primary motor cortex and corticospinal tracts with preservation of lower motor neurons (LMN) has been reported in most cases."

The abstract describes cortical and corticospinal degeneration with LMN preservation.

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Phenotypes

Digestive 1

Dysphagia COMMON Dysphagia (HP:0002015)

Show evidence (1 reference)

PMID:26515619 SUPPORT

"Patients experience stiffness; decreased balance and coordination; mild weakness; and, if the bulbar region is affected, difficulty speaking and swallowing, and emotional lability."

The abstract notes difficulty swallowing when bulbar regions are affected.

Musculoskeletal 1

Spasticity COMMON Spasticity (HP:0001257)

Show evidence (1 reference)

PMID:26515619 SUPPORT

"Patients experience stiffness; decreased balance and coordination; mild weakness; and, if the bulbar region is affected, difficulty speaking and swallowing, and emotional lability."

Stiffness in the abstract reflects spasticity in PLS.

Nervous System 1

Dysarthria COMMON Dysarthria (HP:0001260)

Show evidence (1 reference)

PMID:26515619 SUPPORT

"Patients experience stiffness; decreased balance and coordination; mild weakness; and, if the bulbar region is affected, difficulty speaking and swallowing, and emotional lability."

Difficulty speaking is consistent with dysarthria in PLS.

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Treatments

Supportive Care

Action: supportive care MAXO:0000950

Symptomatic management and supportive interventions.

Show evidence (1 reference)

PMID:26515619 SUPPORT

"Treatment is largely supportive."

The abstract states that management is supportive.

{ }

Source YAML

click to show

name: Primary Lateral Sclerosis
creation_date: '2026-02-02T00:16:36Z'
updated_date: '2026-02-17T21:53:14Z'
category: Complex
parents:
- Motor Neuron Disease
- Neurodegenerative Disease
disease_term:
  preferred_term: primary lateral sclerosis
  term:
    id: MONDO:0018155
    label: lateral sclerosis
description: >-
  Primary lateral sclerosis is a progressive upper motor neuron disorder with
  insidious onset and slow progression.
pathophysiology:
- name: Progressive Upper Motor Neuron Dysfunction
  description: >-
    Degeneration of upper motor neurons leads to slowly progressive spasticity
    and motor impairment without lower motor neuron signs.
  evidence:
  - reference: PMID:26515619
    reference_title: "Primary Lateral Sclerosis."
    supports: SUPPORT
    snippet: "Primary lateral sclerosis is characterized by insidious onset of progressive
      upper motor neuron dysfunction in the absence of clinical signs of lower motor
      neuron involvement."
    explanation: The abstract defines PLS by progressive upper motor neuron
      dysfunction.
- name: Corticospinal Tract Degeneration
  description: >-
    Neuropathology shows degeneration of the primary motor cortex and
    corticospinal tracts with relative preservation of lower motor neurons.
  evidence:
  - reference: PMID:33602010
    reference_title: "Neuropathology of primary lateral sclerosis."
    supports: SUPPORT
    snippet: "Degeneration of the primary motor cortex and corticospinal tracts with
      preservation of lower motor neurons (LMN) has been reported in most cases."
    explanation: The abstract describes cortical and corticospinal degeneration
      with LMN preservation.
phenotypes:
- name: Spasticity
  category: Neurologic
  frequency: COMMON
  phenotype_term:
    preferred_term: Spasticity
    term:
      id: HP:0001257
      label: Spasticity
  evidence:
  - reference: PMID:26515619
    reference_title: "Primary Lateral Sclerosis."
    supports: SUPPORT
    snippet: "Patients experience stiffness; decreased balance and coordination; mild
      weakness; and, if the bulbar region is affected, difficulty speaking and swallowing,
      and emotional lability."
    explanation: Stiffness in the abstract reflects spasticity in PLS.
- name: Dysarthria
  category: Neurologic
  frequency: COMMON
  phenotype_term:
    preferred_term: Dysarthria
    term:
      id: HP:0001260
      label: Dysarthria
  evidence:
  - reference: PMID:26515619
    reference_title: "Primary Lateral Sclerosis."
    supports: SUPPORT
    snippet: "Patients experience stiffness; decreased balance and coordination; mild
      weakness; and, if the bulbar region is affected, difficulty speaking and swallowing,
      and emotional lability."
    explanation: Difficulty speaking is consistent with dysarthria in PLS.
- name: Dysphagia
  category: Neurologic
  frequency: COMMON
  phenotype_term:
    preferred_term: Dysphagia
    term:
      id: HP:0002015
      label: Dysphagia
  evidence:
  - reference: PMID:26515619
    reference_title: "Primary Lateral Sclerosis."
    supports: SUPPORT
    snippet: "Patients experience stiffness; decreased balance and coordination; mild
      weakness; and, if the bulbar region is affected, difficulty speaking and swallowing,
      and emotional lability."
    explanation: The abstract notes difficulty swallowing when bulbar regions
      are affected.
treatments:
- name: Supportive Care
  description: Symptomatic management and supportive interventions.
  treatment_term:
    preferred_term: supportive care
    term:
      id: MAXO:0000950
      label: supportive care
  evidence:
  - reference: PMID:26515619
    reference_title: "Primary Lateral Sclerosis."
    supports: SUPPORT
    snippet: "Treatment is largely supportive."
    explanation: The abstract states that management is supportive.
references:
- reference: DOI:10.1002/1873-3468.12646
  title: <scp>TDP</scp>‐43 and <scp>FUS </scp><i>en route</i> from the nucleus
    to the cytoplasm
  findings: []
- reference: DOI:10.1007/s00415-024-12261-z
  title: 'Supra- and infra-tentorial degeneration patterns in primary lateral sclerosis:
    a multimodal longitudinal neuroradiology study'
  findings: []
- reference: DOI:10.1080/21678421.2020.1837174
  title: Neurophysiological features of primary lateral sclerosis
  findings: []
- reference: DOI:10.1080/21678421.2020.1837176
  title: Neuroimaging in primary lateral sclerosis
  findings: []
- reference: DOI:10.1101/2023.07.19.23292817
  title: Genetic and phenotype analyses of primary lateral sclerosis datasets
    from international cohorts
  findings: []
- reference: DOI:10.1212/wnl.0000000000000090
  title: Progressive hemiparesis (Mills syndrome) with aphasia in amyotrophic
    lateral sclerosis
  findings: []
- reference: DOI:10.3389/fimmu.2017.01005
  title: 'Role of Neuroinflammation in Amyotrophic Lateral Sclerosis: Cellular Mechanisms
    and Therapeutic Implications'
  findings: []
- reference: DOI:10.3389/fimmu.2022.924734
  title: Divergent complement system activation in two clinically distinct
    murine models of multiple sclerosis
  findings: []
- reference: DOI:10.3389/fnagi.2022.892518
  title: Towards Understanding the Relationship Between ER Stress and Unfolded
    Protein Response in Amyotrophic Lateral Sclerosis
  findings: []
- reference: DOI:10.3389/fnagi.2023.1047897
  title: Potential roles of the endoplasmic reticulum stress pathway in
    amyotrophic lateral sclerosis
  findings: []
- reference: DOI:10.3389/fncel.2015.00041
  title: 'Oxidative stress and mitochondrial damage: importance in non-SOD1 ALS'
  findings: []
- reference: DOI:10.3389/fncel.2025.1671419
  title: 'TDP-43-proteinopathy at the crossroads of tauopathy: on copathology and
    current and prospective biomarkers'
  findings: []
- reference: DOI:10.3389/fnins.2015.00448
  title: Golgi Fragmentation in ALS Motor Neurons. New Mechanisms Targeting
    Microtubules, Tethers, and Transport Vesicles
  findings: []
- reference: DOI:10.3389/fnins.2019.01310
  title: 'ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now?'
  findings: []
- reference: DOI:10.3389/fnins.2023.1189470
  title: Current insights in the molecular genetic pathogenesis of amyotrophic
    lateral sclerosis
  findings: []
- reference: DOI:10.3389/fnmol.2017.00263
  title: 'Autophagy Dysregulation in ALS: When Protein Aggregates Get Out of Hand'
  findings: []
- reference: DOI:10.3389/fnmol.2020.00078
  title: Dysregulation of RNA-Binding Proteins in Amyotrophic Lateral Sclerosis
  findings: []
- reference: DOI:10.3389/fnmol.2022.1000183
  title: 'Synaptic dysfunction in ALS and FTD: anatomical and molecular changes provide
    insights into mechanisms of disease'
  findings: []
- reference: DOI:10.3389/fnmol.2023.1172197
  title: 'Common mechanisms underlying axonal transport deficits in neurodegenerative
    diseases: a mini review'
  findings: []
- reference: DOI:10.3390/jcm13020578
  title: 'Primary Lateral Sclerosis: An Overview'
  findings: []
- reference: PMID:31036551
  title: Amyotrophic lateral sclerosis mutant TDP-43 may cause synaptic
    dysfunction through altered dendritic spine function.
  findings: []
- reference: PMID:38891774
  title: Revisiting Glutamate Excitotoxicity in Amyotrophic Lateral Sclerosis
    and Age-Related Neurodegeneration.
  findings: []

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