MRI Changes in Juvenile Ceroid Lipofuscinosis
MRI abnormalities are present in 100% of patients with juvenile neuronal ceroid lipofuscinosis (JNCL) who undergo brain imaging, though the severity and specific patterns vary with disease stage and patient age. 1, 2
Universal MRI Findings
All patients with JNCL demonstrate diffuse cerebral atrophy on MRI, making this the most consistent neuroimaging feature of the disease. 2 However, the timing and severity of atrophy progression correlates with age:
- Mild to moderate cerebral atrophy develops in approximately 47% (14 of 30) of patients, predominantly affecting those over 14 years of age 1
- Cerebellar atrophy occurs in 40-55% of JNCL patients, with higher rates (55%) specifically in the juvenile subtype compared to other NCL variants 2
- Progressive hippocampal atrophy occurs at an annual rate of 3.3% volume loss, exceeding the 2.9% whole brain atrophy rate and the 2.4% gray matter loss rate 3
White Matter and Deep Gray Matter Changes
Cerebral leucoencephalopathy (white matter signal abnormalities) appears in 45-65% of JNCL patients, representing the most significant measurable alteration even in the youngest patients. 1, 2 The white matter shows increased T2/FLAIR signal intensity with statistical significance (P < 0.0001) compared to age-matched controls. 1
Thalamic T2-weighted hypointensity develops in 33-36% of JNCL patients, typically appearing from age 7 years onward. 1, 2 This finding is less frequent in juvenile-onset disease compared to infantile-onset NCL (where it occurs in 80% of cases). 2
The caudate nucleus and putamen also demonstrate low signal intensity on T2-weighted imaging, appearing from ages 11 years onward. 1
Additional Characteristic Features
Recent expanded phenotyping has identified previously underreported findings in genetically confirmed NCL cases:
- T2/FLAIR hyperintensity in the posterior limb of internal capsule (present in 22 of 24 patients in one series) 4
- Abnormal signal in the ventral pons (79% of cases) 4
- Insular and subinsular region signal abnormalities (75% of cases), a finding reported for the first time in 2020 4
- Periventricular and parieto-occipital white matter hyperintensities are particularly characteristic of late-infantile NCL but can occur in juvenile forms 2
Corpus Callosum and Brainstem Involvement
Reduction in the size of both the corpus callosum and brainstem structures occurs consistently in JNCL, though these changes may be subtle early in disease. 1
Clinical Correlation and Diagnostic Timing
Critical pitfall: MRI findings develop relatively late in JNCL, with the absence of pathological findings in very early disease stages being an important diagnostic consideration. 1 The median delay between disease onset and diagnosis is 1.5 years, with mean ages of disease onset at 4.7 years, first MRI at 6.8 years, and diagnosis at 7.3 years. 4
The MRI findings correlate significantly with clinical severity markers including decreased intelligence, speech disturbances, and motor problems, making them useful for assessing disease severity and prognosis, particularly in younger patients. 1
Progressive Nature
Follow-up imaging demonstrates progressive changes in 89% (8 of 9) of patients with serial MRI studies, with both atrophy and white matter signal abnormalities worsening over time. 4 The hippocampal volume loss of 0.85 cm³ over 5 years represents one of the most quantifiable progressive changes. 3