The fact that a child has a white matter disorder is detected by means of imaging, usually Magnetic Resonance Imaging (MRI). Following the detection of this white matter disorder, it is important to try to identify its cause. Without identification of the cause, there is no information on whether the disease is acquired or inherited, whether there is effective treatment, and what the prognosis is.
In the search for the cause of a disease, the clinical history, the family history, and findings at physical examination are the most important items to start with. It makes a difference whether the disease is slowly progressive, subacute and monophasic, or episodic. Provoking factors tell us a lot about the possible causes. Presence of similarly affected family members or consanguinity in the family tells us something about the possible mode of inheritance. The findings at physical examination are also very important. Not only the neurological findings matter. The presence of abnormalities of other organs, such as the eyes, ears, heart, liver, spleen, sexual organs, and skin, provide important diagnostic clues.
Magnetic Resonance Imaging
For us, the next step is detailed analysis of the MRI available. The diagnosis "white matter disorder" is made through MRI, so the MRI is already available. Systematic analysis of the images provides important diagnostic information. We call the process of systematic MRI analysis and interpretation "MRI pattern recognition".
In the late eighties we found out that it makes a difference which white matter structures of the brain are affected and which are spared, in which sequence they are affected, whether there are also gray matter abnormalities and whether there is contrast enhancement. We set up a large study in which we analyzed many MRI's of patients with a white matter disorder with a known cause. We demonstrated that each disease or each category of disorders had its own specific combination of MRI abnormalities, that is to say: its own specific pattern. This information contained in each MRI can be used to advantage in the diagnostic process. First of all, MRI helps in the diagnostic decision whether we most likely are dealing with an inherited or acquired disorder. Inherited disorders usually have a symmetrical pattern of abnormalities, whereas asymmetrical patterns are most commonly observed in acquired disorders. Inherited white matter disorders are usually confluent, while multifocal white matter abnormalities are more commonly seen among the acquired disorders. Of course, there are exceptions to these rules. More detailed analysis of the images will help to make a list of most likely inherited or acquired disorders. Some physicians seem to think these is a standard list of tests to be performed in white matter disorders in children, when inherited conditions are most likely. We do not agree with that. MRI gives so much information, that sometimes one test is sufficient for a final diagnosis.
Tests commonly performed when it is likely that the white matter disorder is inherited, include assessment of urine and plasma amino acids and organic acids, assessment of blood and CSF levels of lactate and pyruvate, assessment of the activities of several lysosomal enzymes in white blood cells, assessment of the blood levels of very long-chain fatty acids and phytanic acid, analysis of mitochondrial DNA, and assessment of mitochondrial function in (preferably) fresh muscle tissue. Other important tests are analysis of hormone levels, especially adrenal hormones, assessment of levels of vitamins, and analysis of the DNA repair processes. It may be important to study conduction velocity of peripheral nerves to see whether not only the central nervous system is affected but also the peripheral nerves. It is often important to evaluate the function of other organs than the nervous system, including the ears, eyes and internal organs.