Leukoencephalopathies in mitochondrial disorders: clinical and MRI findings

Area of Science:

• Neurology
• Mitochondrial Biology
• Neuroimaging

Background:

• The central nervous system (CNS) is the second most commonly affected organ in mitochondrial disorders (MIDs).
• White matter lesions (WMLs) are frequent CNS abnormalities in MIDs, termed leukoencephalopathies in mitochondrial disorders (LEM).
• LEM morphology varies significantly, even within the same MID type or family, and can be present with or without neurological symptoms.

Purpose of the Study:

• To highlight the significance of leukoencephalopathies in mitochondrial disorders (LEM) as a key CNS manifestation.
• To emphasize the diagnostic challenges and prognostic implications of LEM in MIDs.
• To advocate for routine cerebral imaging in all MID patients, irrespective of clinical CNS presentation.

Main Methods:

• Review of imaging findings in patients with mitochondrial disorders.
• Analysis of the morphological characteristics of white matter lesions (WMLs) in the CNS.
• Differential diagnosis considerations for LEM.

Main Results:

• White matter lesions (WMLs) in MIDs are likely caused by metabolic defects or oxidative stress, leading to neuronal death and glial replacement.
• LEM can be misinterpreted, especially when the mitochondrial defect is not obvious in other organs or when MID is not considered.
• Accurate diagnosis of LEM requires confirming an MID, detecting WMLs, and excluding other causes.

Conclusions:

• Leukoencephalopathies in mitochondrial disorders (LEM) significantly impact the prognosis of mitochondrial disorders (MIDs).
• All patients diagnosed with MIDs should undergo cerebral imaging to detect potential LEM, even without apparent clinical CNS signs.
• Early identification of LEM through imaging is vital for appropriate patient management and prognosis assessment.