Adult Leukodystrophies: A Step-by-Step Diagnostic Approach

Abstract

Leukodystrophies usually affect children, but in the last several decades, many instances of adult leukodystrophies have been reported in the medical literature. Because the clinical manifestation of these diseases can be nonspecific, MRI can help with establishing a diagnosis. A step-by-step approach to assist in the diagnosis of adult leukodystrophies is proposed in this article. The first step is to identify symmetric white matter involvement, which is more commonly observed in these patients. The next step is to fit the symmetric white matter involvement into one of the proposed patterns. However, a patient may present with more than one pattern of white matter involvement. Thus, the third step is to evaluate for five distinct characteristics-including enhancement, lesions with signal intensity similar to that of cerebrospinal fluid, susceptibilityweighted MRI signal intensity abnormalities, abnormal peaks at MR spectroscopy, and spinal cord involvement-to further narrow the differential diagnosis. ©

Sensitivity to myelin using model‐free analysis of the water resonance line‐shape in postmortem mouse brain

“…3 Clinical application of MRI employed to aid in the diagnosis of these disorders typically involves a patternrecognition approach involving the presentation of relative gray/white matter contrast compared across some combination of T 1 weighted, T 2 weighted, T 1 weighted/T 2 weighted, and FLAIR acquisitions. [4][5][6][7] Based on "normal" expected gray/white matter contrast, these different contrast-weighting approaches can be leveraged against one another to make some qualitative assessment of the health of the white matter and the underlying myelin. While clinically useful, these approaches lack specificity to myelin content or integrity.…”

Seizures and early onset dementia: D2HGA1 inborn error of metabolism in adults

“…However, the absence of typical clinical or additional imaging features specific for these entities would help to exclude them; also, the presence of subependymal nodules is a unique feature that has not been described in these other leukodystrophies. 7 Childhood cases of D2HGA1 have shown subcortical leukodystrophy with variable basal ganglia involvement 3 which still differs from white matter involvement in TS.…”

“…In this case, preferential involvement of the frontal white matter could raise an imaging differential diagnosis of Alexander disease, frontal variant of x‐linked adrenoleukodystrophy, metachromatic leukodystrophy or leukoencephalopathy with axonal spheroids and pigmented glia. However, the absence of typical clinical or additional imaging features specific for these entities would help to exclude them; also, the presence of subependymal nodules is a unique feature that has not been described in these other leukodystrophies 7 . Childhood cases of D2HGA1 have shown subcortical leukodystrophy with variable basal ganglia involvement 3 which still differs from white matter involvement in TS.…”

Clinical Reasoning: A 42-year-old woman with progressive cognitive difficulties and gait imbalance

“…Once an adult-onset leukodystrophy is suspected, the differential diagnosis can be narrowed down based on MRI T2/fluid-attenuated inversion recovery (FLAIR) pattern of abnormalities, additional radiologic clues, and associated clinical features. [6][7][8] Ascertaining the diagnosis requires specific biochemical assays and genetic testing (the most commonly affected genes are italicized). Brain biopsy may be indicated in some clinical contexts.…”

“…Specific clinical features (e.g., peripheral neuropathy, adrenal insufficiency) and imaging characteristics can help identify the type of leukodystrophy (figure 3). [6][7][8] In ALSP, the WMLs are usually bilateral, but are not always symmetrical or confluent. The periventricular and subcortical white matter of the frontal lobes is commonly involved.…”