Diagnosing “undiagnosed” leukodystrophies

Over the past few decades, an increasing number of previously undiagnosed leukodystrophies have been identified, mainly due to advances in molecular genetics. Although most leukodystrophies produce symmetric pyramidal tract signs, in particular spasticity, the clinical presentation may be variable, especially in adults. Findings, including ataxia, bulbar or pseudobulbar palsy, peripheral nerve involvement, and dementia, may be isolated, asymmetric, or segmental, such as spastic paraparesis. Fortunately, MRI has proven to be very helpful in defining leukodystrophies, based on its sensitivity in demonstrating abnormalities of myelin development. Using MRI, an unknown leukodystrophy can be classified pathologically into one of three major categories: dysmyelination—abnormal formation of white matter; spongiform or cystic degeneration of myelin; and hypomyelination—delayed or decreased production of myelin. MRI can also provide evidence of involvement of gray matter regions of the brain, such as seen in mitochondrial disorders. Most leukodystrophies produce symmetric and rather diffuse white matter abnormalities, but some disorders seem to have a predilection for particular brain regions that may be helpful in diagnosis. Recent investigations have suggested that diffusion tensor MRI and MR spectroscopy may …