What are the clinical findings for leukoencephalopathy?

Clinical Findings of Leukoencephalopathy

Leukoencephalopathy typically presents with cognitive impairment, behavioral disturbances, and motor dysfunction, with onset commonly in the fourth or fifth decade of life and a clinical presentation that often mimics other neurological disorders. 1

Core Clinical Manifestations

Cognitive Symptoms

• Executive dysfunction
• Attention deficits
• Memory impairment
• Psychomotor slowing
• Progressive cognitive decline 1

Behavioral and Psychiatric Symptoms

• Personality changes
• Behavioral disturbances
• Psychiatric symptoms (including aphasia)
• Mood disorders 2, 1

Motor Symptoms

• Gait disturbance
• Bradykinesia
• Movement disorders (including hemiparesis)
• Motor dysfunction 2, 1

Other Neurological Manifestations

• Seizures (generalized tonic-clonic or partial complex)
• EEG abnormalities in 60-70% of cases 1
• Retrochiasmal visual deficits 2
• Chorea (irregular, involuntary jerky movements) 1

Disease Onset and Progression

• Typically subacute onset (over weeks) rather than acute 2
• Progressive worsening of symptoms 2
• May initially present as a single seizure or severe migraine in some cases 2
• Can present insidiously with slow decline in health 2

Specific Presentations by Type

CSF1R-Related Leukoencephalopathy

• Cognitive impairment
• Behavioral disturbances
• Motor dysfunction
• Onset typically in fourth or fifth decade of life
• May mimic multiple sclerosis, frontotemporal dementia, Parkinson's disease, or atypical parkinsonism 2

Toxic Leukoencephalopathy

• Wide array of neurologic deficits
• Alteration of mental status
• Symptoms reflect location of white matter damage 3, 4
• May be reversible or progressive depending on toxin and exposure 4

Progressive Multifocal Leukoencephalopathy (PML)

• Visual deficits
• Cognitive impairment
• Motor weakness
• In AIDS patients: gait disturbance, dysarthria, dysphasia, and ocular palsy 5

Diagnostic Considerations

Differential Diagnosis

Leukoencephalopathy may mimic:

• Multiple sclerosis
• Frontotemporal dementia
• Parkinson's disease
• Atypical parkinsonism
• Autoimmune encephalitis 2, 1

Clinical Features Distinguishing from Multiple Sclerosis

Feature	Multiple Sclerosis	Leukoencephalopathy (e.g., PML)
Onset	Acute (hours to days)	Subacute (weeks)
Evolution	Stabilizes, may resolve spontaneously	Progressive
Presentation	Diplopia, paresthesia, paraparesis, optic neuritis, myelopathy	Aphasia, behavioral changes, retrochiasmal visual deficits, hemiparesis, seizures [2]

Sex Differences

• Women may have earlier disease onset (40 years vs. 43 years in men) in CSF1R-related leukoencephalopathy 2
• Slightly higher prevalence in women (54%) in CSF1R-related leukoencephalopathy 2

Diagnostic Challenges

• Frequently misdiagnosed in initial stages due to:
  • Heterogeneity of presentation
  • Rarity of the condition
  • Mimicry of more common neurological disorders 2, 1
• Diagnosis often delayed by 2.3 years from symptom onset to neuroimaging 2

Clinical Course and Prognosis

• Some forms (like CSF1R-related leukoencephalopathy) are fatal 2
• Prognosis varies widely depending on etiology
• Some forms may be reversible (especially toxic leukoencephalopathies if the causative agent is removed) 3, 4
• Others may have long-term consequences 1

Early recognition of these clinical manifestations is crucial for timely diagnosis and appropriate management, as some forms may benefit from emerging therapies such as allogeneic stem cell transplantation and microglia replacement therapy 2, 1.