Advances in medical imaging for leukodystrophies described by Pr. Raphael Schiffmann

Written on Friday 12 April 2013

Pr. Schiffmann, pediatric neurologist, former member of the Scientific Committee of the ELA Foundation  and director of the Institute of Metabolic Disease at Baylor in Dallas, TX (USA), describes the advances in medical imaging for leukodystrophies.


When started your interest on myelin disorders and why?

My interest started in 1991 when I saw the first patients with CACH (Childhood Ataxia with CNS Hypomyelination also known as Vanishing White Matter Disease or VWMD) when I was working as a Clinical Fellow at the National Institute of Neurological Disorders and Stroke, National Institute of Health (NIH),  in Bethesda, Maryland, USA.

After describing this disease I established at NIH a clinical research protocol to study the leukodystrophies of unknown cause. That protocol led, among other findings, to the identification of 3 novel leukodystrophy syndromes.


How helpful is the MRI technology for the diagnosis of these type of diseases?

MRI was and still is absolutely critical for the diagnosis of leukodystrophies. The unusual abnormalities on MRI were initially the center of the clinical definition of CACH. To this day, the pattern of abnormalities on the MRI is the most useful diagnostic tool in the leukodystrophies.


How has evolved the MRI technology over the years?

MRI technology progressively improved over the years with better quality and resolution of the images and the addition of different ways (sequences) to look at the brain. The introduction of MRI to the diagnosis of the leukodystrophies was further facilitated by pioneering work of people such as Pr. Marjo S. van der Knapp in Amsterdam.


Nowadays what can be detected using the new MRI tools ?

The most important for the leukodystrophies are still the traditional T1-, T2-weighted and FLAIR images. They help us detect and classify the existence of a white matter disease and point to the correct diagnostic possibilities. DTI and MRS are somewhat helpful in further defining the pattern of abnormalities but are not critical in most cases. Note that for detection of calcifications in the brain that occur in a number of leukodystrophies, CT scan is still the most sensitive and thus useful tool.


How did all these discoveries impact the lives and care of the patients?

The main advance so far is better diagnosis of patients with leukodystrophies. Knowing the exact cause is very important to most affected families – it is important to know precisely what you are up against. Knowing the exact molecular diagnosis makes genetic counseling and therefore family decisions a lot easier. Therapies of these diseases always lag behind our ability to diagnose them. I am confident that over the coming years treatments will be developed for most if not all of the leukodystrophies. When that happens, it will be very important to “connect” the patient with a specific diagnosis with the appropriate therapy (or initially treatment trial) for that disorder.


How do you see the field advancing in the future?

We are now at the stage of a growing push for specific and also non-specific but effective therapies for the leukodystrophies. Over the coming years, diagnosis will be made simpler, cheaper and more rapid because of better molecular genetic techniques. Natural history of each disease will be studied systematically and progressively we will be able to translate our knowledge to efficacious therapies. In most cases however, these therapies will have to be instituted very early in the disease process in order to be truly effective.