Leukoencephalopathy or leukodystrophy is characterized pathologically by extensive degenerative and/or demyelinating lesions in cerebral white matter and produces various clinical manifestations such as behavioral and/or mood changes, dementia, motor impairment and epilepsy. The hereditary form of this disease is rare, but recent advances in diagnostic techniques have made it possible to make a correct pre-mortem diagnosis for some diseases including CADASIL and CARASIL. Recently, another unique form of the disease, hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) has been noted. The clinical picture of HDLS is as follows: age of onset ranging from 8 to 78 years (average: 39 years), autosomal dominant inheritance, and dementia. The presence of numerous neuroaxonal spheroid in cerebral white matter is one of the pathologic hallmarks of HDLS. Another term "familial pigmentary orthochromatic leukodystrophy (POLD)" has been also used for the patients showing similar clinical pictures and pathologic findings of the patients. Both disorders are now regarded as a single disease entity. Rademakers et al have just reported that HDLS is caused by mutation in the colony stimulating factor 1 receptor gene (CSF1R) and HDLS should be included in the differential diagnosis of familial occurrence of pre-senile dementia.